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Withdrawal Assessment Tool–1 (WAT–1): An assessment instrument for monitoring opioid and benzodiazepine withdrawal symptoms in pediatric patients

Withdrawal Assessment Tool–1 (WAT–1): An assessment instrument for monitoring opioid and benzodiazepine withdrawal symptoms in pediatric patients - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Questionnaires, Related


The Withdrawal Assessment Tool–1 (WAT–1): An assessment
instrument for monitoring opioid and benzodiazepine withdrawal
symptoms in pediatric patients*
Linda S. Franck, PhD, RN, RGN, RSCN, FRCPCH, FAAN; Sion Kim Harris, PhD;
Deborah J. Soetenga, RN, MS, CCNS; June K. Amling, RN, MSN, CCRN; Martha A. Q. Curley, RN, PhD, FAAN
P
atients in the pediatric inten-
sive care unit (PICU) fre-
quently receive prolonged an-
algesia and sedation to
provide pain relief and blunt physio-
logic stress responses (1–3). Iatrogenic
withdrawal occurs when these drugs
are then stopped abruptly or weaned
too rapidly, causing central nervous
system hyperirritability, autonomic sys-
tem dysregulation, gastrointestinal dys-
function, and motor abnormalities (4,
5). The risk of withdrawal is influenced
by the length and amount of exposure
to opioids and benzodiazepines, rising
to over 50% after 5 days of continuous
infusion or around-the-clock adminis-
tration (6). Iatrogenic withdrawal can
complicate medical treatment, cause
distress to patients and families, and
prolong recovery and hospital stay (1, 4, 7).
Although the prevalence of iatrogenic with-
drawal is unknown, one survey found it was
a problem in 94% of PICUs (8).
Despite the fact that iatrogenic with-
drawal has been observed for over 20 yrs
in infants and children receiving inten-
sive care, a gold standard for the diagno-
sis of withdrawal does not exist. Without
a measurement tool, early diagnosis and
systematic evaluation of the effectiveness
of treatment is difficult (2, 5, 6, 9).
Current clinical assessment tools are
derivatives of the Finnegan Neonatal Ab-
stinence Score (NAS) developed in 1975
for the assessment of withdrawal symp-
toms in otherwise healthy neonates with
prenatal drug exposure (10). Our previ-
ous investigation of the Opioid and Ben-
zodiazepine Withdrawal Score (OBWS)
provided preliminary validity and reliabil-
ity of a withdrawal assessment measure
for use with infants and young children
in intensive care settings (6, 11). When
tested, we found that sensitivity and spec-
Objective: To develop and test the validity and reliability of the
Withdrawal Assessment Tool–1 for monitoring opioid and benzo-
diazepine withdrawal symptoms in pediatric patients.
Design: Prospective psychometric evaluation. Pediatric critical
care nurses assessed eligible at-risk pediatric patients for the pres-
ence of 19 withdrawal symptoms and rated the patient’s overall
withdrawal intensity using a Numeric Rating Scale where zero indi-
cated no withdrawal and 10 indicated worst possible withdrawal.
The 19 symptoms were derived from the Opioid and Benzodiazepine
Withdrawal Score, the literature and expert opinion.
Setting: Two pediatric intensive care units in university-affili-
ated academic children’s hospitals.
Patients: Eighty-three pediatric patients, median age 35 mos
(interquartile range: 7 mos�10 yrs), recovering from acute respi-
ratory failure who were being weaned from more than 5 days of
continuous infusion or round-the-clock opioid and benzodiaz-
epine administration.
Interventions: Repeated observations during analgesia and
sedative weaning. A total of 1040 withdrawal symptom assess-
ments were completed, with a median (interquartile range) of 11
(6–16) per patient over 6.6 (4.8�11) days.
Measurements and Main Results: Generalized linear modeling
was used to analyze each symptom in relation to withdrawal
intensity ratings, adjusted for site, subject, and age group. Symp-
toms with high redundancy or low levels of association with
withdrawal intensity ratings were dropped, resulting in an 11-
item (12-point) scale. Concurrent validity was indicated by high
sensitivity (0.872) and specificity (0.880) for Withdrawal Assess-
ment Tool–1 > 3 predicting Numeric Rating Scale > 4. Construct
validity was supported by significant differences in drug expo-
sure, length of treatment and weaning from sedation, length of
mechanical ventilation and intensive care unit stay for patients with
Withdrawal Assessment Tool–1 scores > 3 compared with those
with lower scores.
Conclusions: The Withdrawal Assessment Tool–1 shows ex-
cellent preliminary psychometric performance when used to as-
sess clinically important withdrawal symptoms in the pediatric
intensive care unit setting. Further psychometric evaluation in
diverse at-risk groups is needed. (Pediatr Crit Care Med 2008; 9:
573–580)
KEY WORDS: drug withdrawal symptoms; opioid analgesia; ben-
zodiazepine; sedation
*See also p. 654.
From the Institute of Child Health (LSF), University
College London and Great Ormond Street Hospital for
Children NHS Trust, London, United Kingdom; Children’s
Hospital Boston (SKH, MAQC), Boston, MA; Harvard
Medical School (SKH), Boston, MA; Children’s Hos-
pital of Wisconsin (DJS), Milwaukee, WI; Children’s
National Medical Center (JKA), Washington DC; and
University of Pennsylvania School of Nursing
(MAQC), Philadelphia, PA.
The authors have not disclosed any potential con-
flicts of interest.
Supported, in part, by NIH 1R21HD045020 and
Gustavus and Louise Pfeiffer Research Foundation.
For information regarding this article, E-mail:
l.franck@ich.ucl.ac.uk
Copyright ? 2008 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/PCC.0b013e31818c8328
573Pediatr Crit Care Med 2008 Vol. 9, No. 6

ificity of the OBWS were only moderate
compared with nurses’ clinical judgment
of withdrawal intensity, and we identified
several usability difficulties, including
the need for further training, and im-
proved inter-rater reliability, confusion
over when to assess the patient and the
burden of the frequency of assessment.
The Neonatal Withdrawal Index (NWI)
(12) uses a different approach and has
demonstrated improved diagnostic accu-
racy for detecting withdrawal in neonates
with perinatal drug exposure. The NWI is
performed only twice per day and in-
volves assessment of a brief list of key
withdrawal signs and symptoms before,
during, and after a routine standard phys-
ical assessment and care- giving proce-
dure. This has advantages over previous
methods of 4-hourly observation of the
patient in a “resting” state in terms of
ease of use and efficiency. Moreover, it
minimizes variability associated with dif-
ficulty in defining a resting state, stan-
dardizes the observation, and reduces the
bias that occurs with frequent serial mea-
surement. We hypothesized that the pro-
cedures and structure of the NWI could
provide the basis for a new method of
iatrogenic withdrawal assessment that
had improved reliability, validity, and
ease of use in diagnosing withdrawal in
older infants and children receiving in-
tensive care. We describe here the devel-
opment and preliminary psychometric
evaluation of the new Withdrawal Assess-
ment Tool–1 (WAT–1) for use with criti-
cally ill children who are exposed to opi-
oids and benzodiazepines for prolonged
periods.
MATERIALS AND METHODS
Design. A multicenter prospective repeated
measures study was conducted to evaluate and
refine an instrument developed to assess iat-
rogenic withdrawal symptoms in pediatric
critical care patients. Psychometric evaluation
of the new measure included examining re-
sponse distributions overall and by age, inter-
item redundancy, factor structure, and con-
struct validity by comparing scores across
groups that were expected to differ (known-
groups validity), and analyzing the association
of scores with other clinical variables (e.g.,
amount of drug exposure and length of wean-
ing) hypothesized to be indicative of with-
drawal severity (concurrent and predictive va-
lidity).
Patient Enrollment. The study was con-
ducted within the context of a clinical trial
testing a sedation management protocol in
pediatric patients (2 wks–18 yrs of age) sup-
ported on mechanical ventilation for acute
respiratory failure in the PICU of two chil-
dren’s hospitals (Children’s Hospital National
Medical Center, Washington, DC; Children’s
Hospital of Wisconsin, Milwaukee, WI) (13).
Both PICUs are large (22–24 bed) university-
affiliated regional referral centers. Neither site
had a structured sedation weaning policy in
place. The Institutional Review Boards at both
sites approved the study. Consent for data col-
lection was obtained from all parents/guard-
ians at one site and waived at the other. Data
were collected from February 2004 to April
2006.
All patients exposed to greater than 5 days
of continuous infusion or regular around-the-
clock dosing of opioids were assessed for with-
drawal symptoms twice daily at 8 AM and 8 PM
(and at other times if clinically indicated) from
the day that opioid weaning started until 72
hrs after the last opioid dose (1). The morning
and the highest other score were used in anal-
yses. Patients exited the study at PICU dis-
charge or after 28 days.
Instrument Description. The 19 symptoms
of opioid and benzodiazepine withdrawal were
derived from the OBWS, documented in the
withdrawal literature (1, 4) and supported by
our previous study of withdrawal symptoms in
the PICU setting (11). The 19-item assessment
consisted of 1) a review of the patient’s record
for the past 12 hrs, 2) direct observation of the
patient for 2 mins, 3) patient assessment dur-
ing a progressive stimulus (14) exam routinely
performed to assess level of consciousness at
the beginning of each 12-hr shift, and 4) as-
sessment of poststimulus recovery. The proce-
dure for the standard progressive stimulation
has been previously reported (14). During nor-
mal care, the nurse first calls the patient’s
name in a calm voice. If the patient does not
respond, the nurse calls the patient’s name
and gently touches the patient’s arm or leg. If
the patient still does not respond, the nurse
would assess the patient during a planned nox-
ious procedure, e.g., endotracheal suctioning
or repositioning. Patient data assessed from
the previous 12 hrs included five items: any
loose or watery stools, any vomiting/wretch-
ing/gagging, temperature �37.8°C, respira-
tory rate greater than the child’s baseline, and
suctioning more than once every 2 hrs. Pa-
tient data assessed during the 2-min prestimu-
lus/quiet observation included five items: dis-
tressed state behavior, any tremor, sweating,
uncoordinated or repetitive movements, and
yawning or sneezing. Patient data assessed
during the 1-min progressive stimulus obser-
vation included eight items: startle to touch,
pupils greater than 4 mm, increased muscle
tone, distressed state behavior, any tremor,
sweating, uncoordinated or repetitive move-
ments, and yawning or sneezing. The post-
stimulus recovery data included one item, the
time to regain a calm state. Patients received
one point for any of the observations. Time to
regain a calm state was scored 0 points for 0–2
mins; 1 point for 2–5 mins; and 2 points for
more than 5 mins.
Bedside nurses received training by the
clinical nurse specialist on how to evaluate the
presence or absence of each of the 19 symp-
toms. Training consisted of a didactic review
of the data collection instrument followed by
completion of a posttest. Inter-rater agree-
ment for withdrawal assessment ratings was
established at the start of the study, and re-
evaluated every 3 months by simultaneous
scoring by the clinical nurse specialist and the
patient’s bedside nurse. There was good inter-
rater reliability for the 30 sets of paired ratings
(Cohen’s kappa � 0.80; intraclass correla-
tion � 0.98).
Nurses were also asked to give, based on
their clinical experience and judgment, a sin-
gle overall rating of withdrawal severity on a
0–10 Numeric Rating Scale (NRS), with zero
indicating no withdrawal and 10 indicating
the worst possible withdrawal symptoms.
Nurses’ clinical judgment of withdrawal inten-
sity is the current standard of care.
Additional Data. Demographic and clinical
data included site, age, ethnicity, mortality
risk (Pediatric Risk of Mortality Score) (15),
functional morbidity and cognitive impair-
ment (16), cumulative and peak daily opioid
dosage (morphine equivalents per kg of body
weight), cumulative and peak daily benzodiaz-
epine dosage (midazolam equivalents per kg of
body weight), and administration of any other
analgesia, sedation, or psychoactive medica-
tions. Conversion of opioids and benzodiaz-
epines to morphine and midazolam equiva-
lents was performed according to standard
methods (17). Length of mechanical ventila-
tion, length of PICU stay and length of hospi-
tal stay, all as number of days, were calculated
after discharge or 28 days.
Data Analysis. Descriptive statistics such
as mean and SD, or median and interquartile
range (IQR), were computed for all demo-
graphic and clinical variables, and examined
as to whether they differed by site. The median
(IQR) length of the preweaning and weaning
phases of opioid and benzodiazepine therapy
were computed. The start of the weaning pe-
riod was defined as the first date of a decrease
in daily dosage �10% after five consecutive
days of opioid treatment. All analyses compar-
ing groups were conducted using chi-square
for categorical variables or one-way analysis of
variance or its nonparametric equivalent, the
Mann-Whitney U test, for continuously-
distributed variables. Most statistical analyses
were performed using SPSS 15 (SPSS, Chi-
cago, IL). For analyses that included multiple
observations on the same patient, we used
SUDAAN v. 9.0 analysis software (Research
Triangle Institute, NC) to account for poten-
tial intracluster correlation of data within site
and within patient.
To evaluate the utility of each withdrawal
symptom and identify any that could be
dropped, we first examined the interitem
agreement between prestimulus and stimulus
ratings of the same symptoms (state, tremor,
sweating, movement, yawning) using kappa
574 Pediatr Crit Care Med 2008 Vol. 9, No. 6

coefficient to determine level of redundancy. A
high kappa (�65) indicated redundancy be-
tween the prestimulus and stimulus rating of
a particular symptom, and only one of the two
was chosen to be retained for that symptom.
In addition, we examined the prevalence of
each symptom across groups that we expected
to differ based on nurses’ clinical impression.
Using data from all observations, we compared
symptom prevalence across the following
three groups using the chi-square test in
SUDAAN: those with NRS of 0 (no with-
drawal), 1–3 (possibly in withdrawal), and 4 or
higher (top 20th percentile of scores, likely in
withdrawal). We assessed whether any symp-
toms had relatively high prevalence among
the “no withdrawal” group or did not differ-
entiate the “no withdrawal” and “likely in
withdrawal” groups, indicating that these
symptoms may not be specific to withdrawal.
We also examined the level of missing data for
each item to identify those symptoms that
may be more difficult to assess.
After dropping redundant, nonspecific, or
difficult to assess items, exploratory factor
analyses were performed on the remaining
items using principal components analysis
with varimax rotation to examine structural
validity of the new WAT-1. Based on a scree
plot of initial eigenvalues, we examined three-
factor and four-factor solutions for the total
data set containing all assessments, for each
age group separately, and for two data subsets
created by randomly selecting a single record
per patient.
Construct validity of the WAT-1 was eval-
uated by examining the degree to which peak
WAT-1 scores per patient correlated with
other indicators of the likelihood of with-
drawal, including preweaning cumulative opi-
oid and benzodiazepine exposure, analgesia
and sedative treatment during weaning, and
the duration of weaning. As the data distribu-
tions were often skewed for these variables, we
examined zero-order correlations among vari-
ables by generating Spearman’s rho coeffi-
cients in SPSS.
RESULTS
Patient Characteristics. Among a total
of 245 pediatric patients with acute respi-
ratory failure supported on mechanical
ventilation, data were excluded for 26 pa-
tients who died and for four who did not
commence weaning from analgesia or se-
dation during the 28-day study period. Of
the remaining 215 patients, 117 (54.4%)
were identified as at risk for withdrawal
(�5 days of regular opioid administra-
tion), and 83 (71%) of them had with-
drawal assessment data for inclusion in
the analyses. In 34 cases, patients at-risk
for withdrawal had no assessments ob-
tained due to PICU transfer (seven cases)
or clinical oversight (26 cases). There
were no significant differences in demo-
graphic characteristics between the at-
risk patients with withdrawal assess-
ments and those without, but assessed
patients had greater cumulative opioid
(median [IQR]: 48.2 [25.5–84.3] vs. 7.5
[4.5–18.7] mg/kg; p � 0.001) and benzo-
diazepine (median [IQR]: 7.6 [4.2–10.4]
vs. 2.3 [1.0–3.5] mg/kg; p � 0.001) expo-
sure, longer lengths of mechanical venti-
lation (median [IQR] � 9.9 [6.7–13.8] vs.
7.1 [4.6–9.3] hrs; p � 0.004) and PICU
stays (median [IQR] � 14.0 [10.0–22.5]
vs. 9.5 [7.0–17.0] days; p � 0.015) than
nonassessed patients.
Clinical and demographic characteris-
tics of the study patients are shown in
Table 1. The demographic characteristics
of patients from the two sites (site 1, n �
47; site 2, n � 36) differed only in race
(site 1, 62% African American vs. site
2, 36%, p � 0.05).
Opioid and Benzodiazepine Weaning.
Characteristics of opioid and benzodiaz-
epine exposure and weaning are shown in
Table 2. The speed of opioid weaning var-
ied considerably across patients, with
one-third characterized by consistent de-
creases in dosage of variable increments
until weaning was completed, another
third characterized by multiple decreases
and increases in dose during the weaning
period, and the final third having single
dosage decreases of greater than 25%,
some of which were followed by periods
where the weaning was slowed or halted.
During the weaning period, 32 (39%)
patients received 1–3 other nonopioid an-
algesic or sedative drugs. However, only
two drugs, ketamine and chloral hydrate
were received by more than 10% of pa-
tients. Patients who received these other
drugs had greater exposure to opioids
(mean peak dose � SD: 10.4 � 4.8 vs.
6.4 � 3.9 mg/kg; p � 0.006; cumulative
dose: 77.8 � 49.3 vs. 49.7 � 40.2 mg/kg;
p � 0.009), but there were no differences
in length of the preweaning or weaning
periods or in benzodiazepine dose or dura-
tion compared with patients who were not
given other drugs. There were no differ-
ences in mean length of opioid or benzodi-
Table 1. Demographic and clinical characteristics (n � 83)
Characteristic Value
Age in months, median (IQR) 35 (7–121)
Age group in yrs (%)
0–2 46
2.1–6 19
Over 6 35
Female (%) 42
Race (%)
African American 50
Caucasian 46
Other 4
PCPC �1 (%) 33
POPC �1 (%) 40
PRISM III (15), median (IQR) 9 (6–16)
Length of mechanical ventilation (days) (1, 2), median (IQR) 9.9 (6.7–13.8)
Length of PICU stay (days) (15), median (IQR) 14 (10–23)
Total length of stay (days) (1), median (IQR) 25 (16–38)
IQR, interquartile range; PCPC, pediatric cerebral performance category; POPC, pediatric overall
performance category; PRISM III, Pediatric Risk of Mortality Score; PICU, pediatric intensive care unit.
Table 2. Opioid and benzodiazepine exposure and weaning
Exposure/Weaning Period Value
Opioid treatment cumulative dose (mg/kg)
a
, median (IQR) 48.2 (25.5–84.3)
Peak opioid dose (mg/kg)
a
, median (IQR) 7.6 (4.2–10.4)
Benzodiazepine treatment cumulative dose (mg/kg)
b
, median (IQR) 24.0 (10.5–62.3)
Peak benzodiazepine dose (mg/kg)
b
, median (IQR) 3.3 (1.9–8.1)
Length of opioid treatment before tapering (days), median (IQR) 6 (5–17)
Length of benzodiazepine treatment before tapering (days), median (IQR) 7 (2–21)
Length of opioid weaning (days from peak), median (IQR) 11 (1–23)
Length of benzodiazepine weaning (days from peak), median (IQR) 10 (2–24)
a
Morphine equivalents;
b
Midazolam equivalents.
IQR, interquartile range.
575Pediatr Crit Care Med 2008 Vol. 9, No. 6

azepine therapy or weaning and no differ-
ences in the mean peak or cumulative
opioid doses between the two sites.
Examination of Individual With-
drawal Symptoms. A total of 1040 with-
drawal symptom assessments were com-
pleted, with a median (IQR) of 11 (6–16)
per patient over 6.6 (4.8�11) days. Con-
current NRS withdrawal intensity ratings
were performed for 816 (78.3%) of the
assessments. Table 3 shows the overall
and age group-specific prevalence rates
for each symptom. There was only a mar-
ginal age effect for the startle-to-touch
symptom (chi-square � 5.1, p � 0.085).
The interim analyses revealed redun-
dancy between the prestimulus and stim-
ulus ratings for sweating, uncoordinated/
repetitive movement, tremor, yawning,
and behavioral state, with kappas ranging
from 0.65 to 0.91 and crude percent
agreement ranging from 92.2% to 98.1%.
Redundant items were dropped from either
prestimulus or stimulus observations to re-
duce patient disturbance and increase ease
of symptom assessment (Table 3). Symp-
toms that occurred with relatively high
prevalence among those with NRS of 0, or
that least differentiated patients who re-
ceived higher NRS withdrawal intensity
scores (top 20th percentile) from those
with lower scores, included elevated respi-
ratory rate, suctioning, and dilated pupils.
Therefore, these three items were dropped.
The resulting measure consisted of 11
items (12-point) scale, which we hence-
forth refer to as the WAT-1 (Table 4). The
correlation between the 19 original symp-
toms and the more parsimonious WAT-1
was 0.947.
Factor Structure. A four-factor solu-
tion provided the best overall conceptual
fit, explaining 58% of the variance in
analysis of all WAT-1 assessments. Motor-
related symptoms (tremor, uncoordinat-
ed/repetitive movements, muscle tone,
and startle) comprised the factor that ac-
counted for the most variance. The sec-
ond factor was comprised of behavioral
state (prestimulus state and return to
calm state), the third factor was auto-
nomic related (temperature and sweat-
ing), and the fourth factor was comprised
of gastrointestinal symptoms (stooling,
vomiting) and yawning. The components
of the factor solutions varied slightly by
age group and explained a total of 61%
(0, 2 yrs), 65% (2.1, 6 yrs), or 56% (�6
yrs) of the variance. The item factor load-
ings were slightly different for children
Table 3. Withdrawal symptoms by age group (adjusted for clustering of observations within site and patient, n � 1040)
Observation Overall 0–2 yrs 2.1–6 yrs �6 yrs
From patient record, previous 12 hrs, % (CI)
Any loose/watery stools 20.1 (15.6, 25.6) 18.4 (12.0, 27.3) 19.9 (12.1, 30.9) 22.0 (14.5, 31.9)
Any vomiting/wretching/gagging 7.6 (4.5, 12.6) 12.3 (6.5, 22.5) 5.9 (2.5, 13.4) 3.2 (1.3, 7.6)
Temperature >37.8°C 25.1 (19.3, 31.9) 19.5 (12.0, 30.2) 18.3 (11.2, 28.4) 34.2 (23.8, 46.3)
Respiratory rate often � baseline for this
child
44.2 (37.0, 51.8) 42.8 (31.7, 54.7) 39.3 (25.6, 54.8) 48.1 (35.7, 60.7)
Required suctioning �1 every 2 hrs 16.7 (11.5, 23.6) 18.2 (9.7, 31.3) 14.5 (7.1, 27.4) 16.1 (9.1, 26.9)
2-min prestimulus observation, % (CI)
State: SBS (14) >�1 or awake distressed 15.8 (11.9, 20.6) 17.8 (12.2, 25.2) 12.9 (7.5, 21.2) 14.9 (8.6, 24.5)
Tremor—moderate/severe 7.9 (5.1, 12.0) 8.8 (4.6, 16.0) 3.2 (1.0, 9.7) 9.1 (4.5, 17.3)
Any sweating 13.2 (8.8, 19.3) 13.3 (7.4, 22.5) 7.0 (2.2, 20.1) 15.9 (7.8, 26.0)
Uncoordinated/repetitive
movements—moderate/severe
5.8 (3.8, 8.8) 9.0 (5.7, 14.0) 0.5 (0.1, 3.9) 4.7 (2.0, 10.5)
Yawning or sneezing—2 or more times 9.1 (6.5, 12.5) 9.9 (5.8, 16.5) 13.4 (6.0, 27.3) 6.1 (3.4, 10.9)
1-min stimulus observation, % (CI)
Startle to touch—moderate/severe
a
8.2 (5.9, 11.3) 10.6 (6.8, 16.1) 10.2 (5.0, 19.7) 4.7 (2.3, 9.0)
Pupils �4mm 19.3 (13.6, 26.6) 13.3 (7.3, 22.8) 19.5 (7.9, 40.4) 25.7 (15.4, 39.8)
Muscle tone—increased 16.6 (12.1, 22.2) 21.1 (13.5, 31.4) 9.7 (3.7, 23.2) 14.7 (8.3, 24.7)
State—SBS (14) ��1 or awake and
distressed
17.6 (13.6, 22.5) 20.9 (15.5, 27.5) 15.6 (8.7, 26.4) 15.0 (8.4, 25.3)
Tremor—moderate/severe 10.3 (7.2, 14.5) 12.6 (7.2, 21.0) 7.0 (2.5, 18.3) 9.3 (5.2, 16.0)
Any sweating 13.3 (8.7, 19.4) 13.7 (7.8, 22.9) 7.5 (2.6, 20.0) 15.4 (7.4, 29.4)
Uncoordinated/repetitive
movements—moderate/severe
7.5 (5.1, 10.7) 10.8 (7.2, 15.9) 4.0 (0.8, 19.6) 5.4 (2.4, 11.8)
Yawning or sneezing—2 or more times 9.1 (6.5, 12.4) 9.9 (5.8, 16.5) 11.8 (5.1, 25.1) 6.9 (3.8, 12.1)
Post-stimulus recovery, % (CI)
Time to gain calm state (SBS [14] < 0)
2–5 minutes 14.6 (10.6, 19.9) 20.2 (13.3, 29.5) 10.2 (5.2, 19.2) 10.6 (6.1, 17.8)
>5 minutes 5.7 (3.7, 9.2) 6.7 (3.7, 12.1) 3.8 (1.0, 13.2) 5.9 (2.5, 13.4)
Total score
WAT-1 � 0 (%)
b
43.9 48.1 48.9 37.2
1 17.2 10.6 17.7 24.2
2 13.6 11.2 14.0 15.9
3 8.6 7.9 8.6 9.3
4 6.1 7.2 4.8 5.4
5 3.6 3.6 3.2 3.7
6 3.6 5.4 1.6 2.4
7� 3.4 6.0 1.2 1.9
Total WAT-1 (median, IQR) 1.0 (0.0–3.0) 1.0 (0.0–3.0) 1.0 (0.0–2.0) 1.0 (0.0–2.00)
WAT-1 peak (median, IQR) 3.0 (2.0–6.0) 4.5 (2.0–7.0) 3.0 (1.5–5.0) 4.0 (2.0–6.0)
WAT-1, Withdrawal Assessment Tool–1; CI, confidence interval; IQR, interquartile range; SBS, State Behavioral Scale.
Normal text � in final WAT–1; Italic � eliminated from WAT-1.
a
Startle to touch: greater than 6 yrs � other age groups, p � 0.09;
b
Total WAT-1 score (%): greater than 6 years � other age groups, p � 0.05.
576 Pediatr Crit Care Med 2008 Vol. 9, No. 6

Table 4. Withdrawal Assessment Tool–1 and Instructions
SBS, State Behavioral Scale.
577Pediatr Crit Care Med 2008 Vol. 9, No. 6

over 6 yrs of age compared with the
younger age groups. For example, in the
older age group, motor- and state-related
symptoms loaded on the same factor and
yawning and startle did not meet the
threshold for inclusion (factor loadings �
0.40) in any factor.
Construct Validity. There was a high
degree of convergence between the
WAT-1 total scores and withdrawal inten-
sity ratings (Spearman’s rho coeffi-
cient � 0.80). Examination of receiver-
operator characteristic curves revealed
that a WAT-1 score of 3 or higher had the
best sensitivity and specificity in relation
to an intensity rating indicating clinically
significant withdrawal, i.e., 4 or higher
(.872 and .880; Fig. 1).
We found that the 53 (64%) patients
with higher peak WAT-1 scores (�3)
had greater cumulative opioid doses
and longer duration of opioid treatment
before tapering (Fig. 2) compared with
the 30 (36%) patients whose symptoms
were less severe (WAT-1 �3; Fig. 2).
Peak WAT-1 scores for each patient cor-
related moderately with the length of
opioid therapy (r � .23, p � 0.04) and
benzodiazepine therapy (r � .23, p �
0.04) before weaning and with the
length of opioid weaning (r � .33, p �
0.003). Opioid weaning was completed
in more patients with peak WAT-1
scores �3 compared with those with
higher peak scores (chi-square � 4.3,
p � 0.04). In addition, patients with
higher peak WAT-1 scores (�3) had a
longer opioid weaning period (median
[IQR], 13.0 [9.0, 18.0] vs. 8.0 [5.0, 12.0]
days; p � 0.004) as well as longer
lengths of mechanical ventilation (me-
dian [IQR], 11.7 [8.2, 15.6] vs. 6.9
[5.4, 9.6] days; p � 0.001), PICU stay
(median [IQR], 17.0 [12.0, 27.0] vs. 10.5
[9.0, 15.0] days; p � 0.001) and hospital
stay (median [IQR], 29.0 [19.0, 42.0] vs.
20.0 [14.0, 28.0] days; p � 0.01) than
those with scores of �3. There were no
differences in WAT-1 scores or intensity
rating related to receiving other non-
opioid or sedative drugs during the
weaning period.
DISCUSSION
Within the context of a clinical trial
where clinical parameters relating to an-
algesic and sedative administration and
patient response were prospectively re-
corded over the duration of therapy, we
were able to examine the psychometric
properties of an instrument to quantify
the prevalence and severity of withdrawal
symptoms in children at high risk for
development of iatrogenic withdrawal.
From these data, we were able to con-
struct a parsimonious instrument, the
WAT-1 and to demonstrate its prelimi-
nary concurrent and predictive validity.
This is the largest prospective investiga-
tion and most comprehensive analysis of
opioid and benzodiazepine withdrawal
symptoms in critically ill children.
The factor structure of the WAT-1
conformed to the main expected symp-
tom clusters of motor disturbance, be-
havioral state disturbance, autonomic
disturbance, and gastrointestinal symp-
toms (1, 4, 5). There were some differ-
ences in the frequency and pattern of
symptoms based on age, which is to be
expected given the differences in physical
maturation across the age span of chil-
dren in this study. Further research is
needed to determine whether these dif-
ferences can be accommodated in a single
withdrawal assessment tool or if different
variants of the tool for children of differ-
ent age groups would provide better di-
agnostic accuracy.
The WAT-1 showed excellent sensitiv-
ity and specificity compared with NRS
overall rating of withdrawal severity and
greater validity than intensity ratings as
demonstrated by its better performance
in relation to known risk factors for iat-
rogenic withdrawal such as opioid expo-
sure and length of therapy. We were un-
able to investigate differences between
opioid and benzodiazepine withdrawal
symptoms, since all patients received
both drugs during the study. However,
the validity analysis suggests that the
WAT-1 is better at detecting symptoms of
opioid rather than benzodiazepine with-
drawal. This is not surprising given that
benzodiazepine withdrawal is often de-
scribed as more subtle and with fewer
symptoms (18).
We were also unable to examine rela-
tionships between the speed of opioid or
benzodiazepine dose tapering and the
emergence of withdrawal symptoms be-
cause of the variability of the weaning
Figure 1. Receiver operator characteristic (ROC) curve: Withdrawal Assessment Tool–1 (WAT-1) and
Numeric Rating Scale (NRS) of withdrawal intensity (n � 816). Area under the curve: 0.944 � 0.008
(SE), confidence interval: 0.928, 0.961, p � 0.001; WAT-1 score of 3 or higher had the best sensitivity
and specificity in relation to NRS withdrawal intensity ratings of 4 or higher (0.872 and 0.880,
respectively).
578 Pediatr Crit Care Med 2008 Vol. 9, No. 6

pattern over the observation periods.
These questions are best investigated in a
clinical trial with withdrawal as the pri-
mary end point, testing two or more dis-
tinct protocols for achieving analgesia
and sedation weaning. Although previous
literature has suggested weaning algo-
rithms for children varying from 10% to
50% of the peak dose at 4, 24 hourly
intervals and the addition or substitution
of other drugs (1, 4, 5, 9), only one pro-
spective trial used the NAS and found no
difference when patients were con-
verted from fentanyl to methadone and
weaned over a 5-day or 10-day period
(19). However, the NAS and its variants
lacks sensitivity for the PICU setting (11), is
burdensome (requiring 2, 4 hourly assess-
ments), and is subject to serial bias.
This study has some limitations, the
most significant of which is the incom-
plete independence of the withdrawal
symptom scoring and withdrawal inten-
sity ratings. Although clinical judgment
is often termed a “tin standard,” no vali-
dated biomarkers of iatrogenic with-
drawal presently exist. The use of poly-
pharmacy may also have confounded the
analyses. However, clinician judgment
about a patient’s immediate medical
needs rightly overrides the need for uni-
formity in practice required for instru-
ment validation. Next, withdrawal symp-
tom intensity may have been related to
the patient’s primary medical condition
and we did not search for these potential
confounders. Finally, the sample does not
represent the entire population of chil-
dren experiencing withdrawal symptoms,
and replications of this study are needed
in different samples and settings. How-
ever, in this initial study evaluating the
psychometric properties of an instru-
ment, having a probability sample (sam-
pling of people) is less important than
having the full range of symptom inten-
sity (sampling of content) represented, as
occurred in this study (20).
The main aims of a withdrawal assess-
ment tool are to improve the detection
and treatment of withdrawal symptoms
before they compromise the patient’s
clinical condition. Since the NAS was
first shown to reduce the treatment time
for neonates with prenatal drug exposure
(10), the superiority of an assessment
tool over subjective clinical assessment
has been assumed but never established
for other patient groups or settings. The
lack of adequate measures of iatrogenic
withdrawal and the need for such tools to
guide clinical practice has been repeat-
edly highlighted (5, 9, 21). The WAT-1 is
a significant improvement over previous
withdrawal symptom assessment scales
in that it has fewer items that can be
more objectively and feasibly measured.
It is performed only twice a day compared
with the usual 6, 12 times per day for
other symptom assessment scales, which
increases the likelihood that it will be
used in clinical practice. The assessment
of the WAT-1 parameters is easily inte-
grated into the standard start-of-shift
nursing assessment. Training can be ac-
complished through brief written in-
struction and bedside demonstration and,
consistent with most clinical activities,
we recommend periodic training updates
and inter-rater reliability checks. Further
research is needed to confirm the cut-off
values for the diagnosis of withdrawal and
decisions about treatment. Trends and
direction of movement in WAT-1 scores
may be more important because of the
highly individualized effects of with-
drawal symptoms on a patient’s clinical
recovery.
In summary, iatrogenic withdrawal is
a common side effect of prolonged seda-
tion in critically ill pediatric patients who
require better methods of assessment and
monitoring. The WAT-1 shows excellent
preliminary psychometric performance
when used to assess clinically important
withdrawal symptoms in the PICU set-
ting. It is also much simpler and efficient
than previous assessment methods. Fur-
ther psychometric evaluation is needed in
other at-risk groups, such as neonatal
intensive care unit patients.
ACKNOWLEDGMENTS
We thank the pediatric critical care
nurses, physicians, the patients, and their
families who supported this study.
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