JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY

Volume 28, Number 2, 2018

ª Mary Ann Liebert, Inc.
Pp. 117–123
DOI: 10.1089/cap.2017.0073

Does Acute Propranolol Treatment Prevent

Posttraumatic Stress Disorder, Anxiety,
and Depression in Children with Burns?

Laura Rosenberg, PhD,1,2 Marta Rosenberg, PhD,1,2 Sherri Sharp, PhD,1,2

Christopher R. Thomas, MD,1,2 Helen F. Humphries, MA,2 Charles E. Holzer, III, PhD,2
David N. Herndon, MD,1,3 and Walter J. Meyer, III, MD1,2
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Abstract
Objective: This study examined whether acute propranolol treatment prevented posttraumatic stress disorder (PTSD),
anxiety, and depression in children hospitalized in the pediatric intensive care unit for large burns. We hypothesized that the
prevalence of PTSD, anxiety, and depression would be significantly less in the propranolol than nonpropranolol groups.
Methods: Children who had previously participated in a randomized controlled clinical trial of acute propranolol and
nonpropranolol controls were invited to participate in long-term follow-up interviews. Eligible participants from 1997 to
2008 were identified from the electronic medical records, and data were collected in 2010–2011. Measures included the
Missouri Assessment of Genetics Interview for Children to assess lifetime PTSD, Revised Children’s Manifest Anxiety Scale
to assess anxiety, and two depression inventories Children’s Depression Inventory and Beck Depression Inventory-II.
Results: Of 202 participants, 89 were in the propranolol group and 113 were nonpropranolol controls. Children were an
average of 7 years postburn. The average total body surface area burned was 56.4 + 15.1% (range = 24%–99%). The mean
dose of propranolol was 3.64 – 3.19 mg/kg per day (range = 0.36–12.12). The duration of propranolol inpatient treatment days
varied, mean days 26.5 – 19.8. The prevalence of lifetime PTSD in the propranolol group was 3.5% and controls 7.2%, but this
difference was not statistically significant. We controlled for administration of pain medications, anxiolytics, and antide-
pressants overall and no significant differences were detected in the rates of PTSD, anxiety, or depression.
Conclusions: The prevalence of PTSD, anxiety, and depression was similar in children who received propranolol acutely and
those who did not. This may be influenced by the standard of care that all children received timely pharmacotherapy for pain
and anxiety management and psychotherapy beginning in their acute phase of treatment.

Keywords: children, burns, propranolol, posttraumatic stress disorder, anxiety, depression

Introduction Edition or DSM-5; American Psychiatric Association 2013). Clinical

experience suggests that PTSD in pediatric burn survivors may result

T he prevalence of posttraumatic stress disorder (PTSD)

among pediatric burn survivors varies greatly. One study found
that the current and lifetime rates were 7% and 30%, respectively
(Stoddard et al. 1989). Some predictors of trauma symptoms in
children recovering from burns include pain (Saxe et al. 2005b;
Stoddard et al. 2006), extent of burn (Saxe et al. 2005b; Drake et al.
2006; Stoddard et al. 2006), and parental distress (Saxe et al. 2005a;
Stoddard et al. 2006). Children who have PTSD often experience
nightmares, flashbacks, avoidance behaviors, and increased arousal
(Diagnostic and Statistical Manual of Mental Disorders, Fifth
from the burn incident and treatment of the burn injury. In contrast,
Schneider et al. (2012) found that the burn injury for a group of adult
victims of a nightclub fire as not predictive of PTSD.
There is limited research on the pharmacological management of
PTSD for children with burns (Donnelly 2003). A few studies in-
vestigated the benefits of antidepressants in ameliorating trauma
symptoms. In a randomized, double-blind study done at this pediatric
burn center, Robert et al. (1999) reported that imipramine was more
helpful in the management of acute stress disorder (ASD) for children
with major burns in comparison to chloral hydrate. In a subsequent

1
Shriners Hospitals for Children-Galveston, Galveston, Texas.
Departments of 2Psychiatry and Behavioral Sciences and 3Surgery, University of Texas Medical Branch, Galveston, Texas.
Previous presentations: Propranolol, a possible treatment to prevent posttraumatic stress disorder (poster presentation). American Academy of Child
& Adolescent Psychiatry, Abstract 3.42, 2011; Does propranolol prevent symptoms of posttraumatic stress disorder (PTSD) in children with large burns
(oral presentation)? Proceedings of the American Burn Association (ABA) 44th Annual Meeting, 33(2): Abstract 119, 2012.

117
 118
randomized controlled trial, no differences were detected between
children with ASD symptoms who received imipramine, fluoxetine,
or placebo. Of clinical relevance, 60% of the children treated with
imipramine and 72% of the children treated with fluoxetine re-
sponded favorably to these medications (Robert et al. 2008).
Recently, research has focused on approaches to prevent the de-
velopment of PTSD. Stoddard et al. (2011) conducted a randomized,
controlled clinical trial to examine whether prophylactic sertraline
prevented PTSD and comorbid depression in children with burns
who were in the acute and reconstructive phases of recovery. Chil-
dren in the sertraline and placebo groups experienced less trauma
symptoms 6 months postburn as measured by The Diagnostic In-
terview for Children and Adolescents (DICA); however, the differ-
ence was not statistically significant. Parental reports indicated that
children in the sertraline group experienced fewer PTSD symptoms
at 2, 3, and 6 months postinjury.
The literature on adults has explored the benefits of propranolol, a
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b-adrenergic antagonist blocker, in preventing PTSD after a trau-
matic event. It has been hypothesized that propranolol may impede
the process of fear conditioning (Pitman 1989; Pitman et al. 2002),
inhibit emotional arousal (Cahill et al. 1994; Pomerantz 2006), and
memory consolidation of traumatic events (Cahill et al. 1994; Pitman
et al. 2002; Pomerantz 2006; McGhee et al. 2009).
Vaiva et al. (2003) reported lower rates of PTSD for adults
treated with acute propranolol (9%) in comparison to individuals
who declined treatment (37.5%). Pitman et al. (2002) investigated
whether propranolol helped prevent PTSD in adults posttrauma.
Although there were no significant differences in the prevalence of
PTSD between the propranolol group and controls, individuals in
the propranolol group showed improvements on physiologic
measures. Similarly, Hoge et al. (2012) concluded that there was no
difference in the rate of PTSD for adults who received propranolol
after a traumatic episode in comparison to individuals who did not.
Adults who closely followed the propranolol treatment protocol
reported improvements in physiological reactivity and heart rate.
Only one study investigated the rate of PTSD in adult burn
survivors who were soldiers deployed to Iraq. No differences were
found in the rates of PTSD between the propranolol (32%) and
matched comparison group (27%) even when controlling for burn
size and severity (McGhee et al. 2009).
Limited research is available on the benefits of propranolol for
children exposed to trauma. Famularo et al. (1988) conducted a
pilot study exploring the benefits of propranolol treatment for
children diagnosed with PTSD after experiencing severe physical
and sexual abuse. Children reported a significant improvement in
PTSD symptoms while they were taking propranolol. Nugent et al.
(2010) conducted a controlled pilot study with children who were
hospitalized as a result of traumatic injury. Children were ran-
domized to a 10-day course of propranolol or placebo. Although
there was no significant difference in the rate of PTSD between
the groups, males in the propranolol group reported fewer PTSD
symptoms at 6 weeks.
In a retrospective review conducted at this pediatric burn center,
Sharp et al. (2010) investigated the prevalence of ASD in children
with major burns who received acute propranolol for 1 month and
nonpropranolol controls. There was no significant difference in the
rate of ASD between the groups (8% propranolol group, 5% controls).
To date, no prospective studies have examined the effectiveness
of acute propranolol in preventing PTSD in children with major
burns. This study is a follow-up investigation to previous research
that examined the prevalence of ASD in children who received
acute propranolol and nonpropranolol controls (Sharp et al. 2010).
ROSENBERG ET AL.
The purpose of this study was to examine whether acute pro-
pranolol prevents the development of lifetime PTSD in children
with large burns. We hypothesized that children treated acutely
with propranolol would be less likely to experience lifetime PTSD
than children in the nonpropranolol control group. Because anxiety
(Stoddard et al. 1989; Donnelly 2003; Thomas et al. 2009) and
depression (Stoddard et al. 1989; Donnelly 2003) often co-occur
after trauma, we investigated whether children who received acute
propranolol were less likely to develop these disorders. It was an-
ticipated that the prevalence of anxiety and depression would be
significantly less for children in the propranolol group.
Methods
Participants
Permission for this study was obtained from the Institutional
Review Board of the University of Texas Medical Branch-
Galveston. This was a Shrine funded project with additional support
from the National Institute on Disability, Independent Living, and
Rehabilitation Research (NIDILRR), formerly National Institute on
Disability and Rehabilitation Research (NIDRR), because some of
the children were invited to participate when they attended their
scheduled NIDILRR appointments at this burn center.
Participants included pediatric burn survivors who participated
in a previous blinded, randomized controlled clinical trial of acute
propranolol and nonpropranolol groups conducted at this pediatric
burn center and had large burns, mostly 40% or greater (Herndon
et al. 2001; Jeschke et al. 2007). Those in the propranolol group
received propranolol for 7 or more days during their acute hospi-
talization in the pediatric intensive care unit (PICU). From the
electronic medical records, a list of 380 eligible participants treated
medically from 1997 to 2008 was obtained. Participants included
children from the United States and Mexico with burn injuries who
were treated medically at this pediatric burn center. Children were
English and Spanish speaking, 6 years of age and older at time of
recruitment, and 2–12 years postburn. Children with cognitive
deficiencies and who did not meet the inclusion criteria were not
recruited for this study.
Measures
DSM-5, PTSD section. According to the DSM-5, individu-
als may experience PTSD after exposure to a traumatic event. The
diagnostic criteria for PTSD involves experiencing one or more
intrusion symptoms, one or two avoidance symptoms, two or more
symptoms of altered cognition and mood, and two or more symp-
toms of increased arousal (DSM-5). These symptoms last >1 month
and cause substantial distress. For this study, the diagnostic criteria
for PTSD from the Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition (DSM-IV; American Psychiatric Asso-
ciation 1994) were used, which requires at least one reexperiencing,
three avoidance, and two increased arousal symptoms for at least
1 month (DSM-IV).
Missouri Assessment of Genetics Interview for Children,
PTSD section. The Missouri Assessment of Genetics Interview
for Children (MAGIC) has semi-structured clinical interviews
based on criteria from the Diagnostic and Statistical Manual of
Mental Disorders Third Edition (DSM-III; American Psychiatric
Association 1980) and DSM-IV for diagnosing psychiatric disor-
ders in children and adolescents. The format is comparable to the
DICA (Reich 2000; Reich and Todd 2002).
 PROPRANOLOL TREATMENT FOR PTSD IN CHILDREN
The interviews for evaluating lifetime PTSD in children and
adolescents were used. The MAGIC-C was developed for children
6–12 years of age and has 47 items, and the MAGIC-A was de-
veloped for use with adolescents 13–17 years old and contains 45
items. The interviews are available in English and Spanish (Reich
and Todd 2002). Research by Todd et al. (2003) suggested that the
MAGIC has appropriate inter-rater reliability and stability for
evaluating attention and depression in pediatrics.
Revised Children’s Manifest Anxiety Scale. The Revised
Children’s Manifest Anxiety Scale (RCMAS) is a 37-item self-
report questionnaire for assessment of the level of anxiety in chil-
dren and adolescents (ages 6–19 years). The measure is available in
English and Spanish. It contains four subscales: physiological
anxiety, worry/oversensitivity, social concerns, and a lie scale. Raw
scores are converted to standard scores, with higher scores indi-
cating higher levels of anxiety. The total anxiety score has a mean
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of 50 and a standard deviation of 10, and the 4 subscales have a
mean of 10 and a standard deviation of 3. Scores that fall one or
more standard deviations above the mean are of clinical relevance.
Reliability and validity of the RCMAS as a measure of chronic
anxiety in children has been well established. For the Total Anxiety
Scale, internal consistency for the RCMAS ranges from 0.83 to
0.85 (Reynolds and Richmond 2005).
Children’s Depression Inventory. The Children’s Depres-
sion Inventory (CDI) is a 27-item self-report, gender normed mea-
sure for assessing current depression in children and adolescents
7–17 years of age. The measure is available in English and Spanish. It
contains five subscales: negative mood, interpersonal problems, in-
effectiveness, anhedonia, and negative self-esteem. Raw scores are
converted to T-scores with a mean of 50 and a standard deviation of
10. A total CDI score and scores on the subscales can be obtained.
Higher scores suggest greater depressive symptomatology and are of
clinical significance. This measure has well-established internal
consistency, test-retest reliability, and validity. Internal consistency
for the CDI ranges from 0.71 to 0.89 (Kovacs 1992).
Beck Depression Inventory-II. The Beck Depression In-
ventory (BDI-II) is a 21-item self-report measure that is used to
identify the severity of depression for adolescents and adults (ages
13 years and older). It was based on criteria from the DSM-IV.
Higher raw scores are indicative of higher levels of distress. This
measure has well-established reliability and validity. Internal
consistency for outpatients was 0.92 and for college students it was
0.93 (Beck et al. 1996).
Design
Pediatric burn survivors who participated in a previous blinded,
randomized controlled clinical trial of acute propranolol and a
nonpropranolol control group (Herndon et al. 2001; Jeschke et al.
2007) and their parents/caregivers were invited to participate in this
study during their clinic appointments at this pediatric burn hospital
or outreach clinics in Mexico. Phone calls were made to contact the
parents/caregivers of children who did not have scheduled clinic
appointments, and the children were given clinic appointments at
an outreach clinic near their community. Data were collected over a
2-year period from 2010 to 2011.
Study personnel included two bilingual psychologists who were
fluent in English and Spanish, a child psychiatrist, and the project
coordinator. Informed consent was obtained from the parent/care-
119
giver, assent was received from the child, and the families were given
a copy of these forms. Burn survivors completed a semi-structured
clinical interview and were administered the MAGIC-C or MAGIC-
A (Reich and Todd 2002) to assess lifetime PTSD. They also com-
pleted self-report measures; for anxiety the RCMAS (Reynolds and
Richmond 2005), and for depression the CDI (Kovacs 1992) or BDI-
II (Beck et al. 1996). The psychologists and psychiatrist were trained
to administer the MAGIC before the implementation of the study.
The psychologists and psychiatrist interviewed English-speaking
children and adolescents. The psychologists familiar with cultural
issues in Mexico interviewed the Spanish-speaking children and
adolescents. When participants had difficulty comprehending ques-
tions, clarification was provided by the person conducting the clin-
ical interview. Completion of the interview and self-report measures
took *1 to 1 ½ hours. The questions on the self-report measures
were read to the children and adolescents who had difficulty reading.
Parents/caregivers provided demographic information.
Information from the electronic medical records, pharmacy re-
cords, and master list of children who participated in the previously
mentioned randomized, controlled clinical trial was used to verify
propranolol status by the project coordinator. The two psycholo-
gists and the child psychiatrist were blind as to the child’s previous
propranolol status. Acute propranolol had been administered based
on weight (target 4 mg/kg per day) and response and titrated to
reduce the pulse rate to normal range for age. Propranolol was
usually started within 48–72 hours of time of acute admission to
this pediatric burn center (Sharp et al. 2010). The average time of
admission to this pediatric burn hospital was 5 – 8 days after the
burn trauma. The mean dose of propranolol was 3.64 – 3.19 mg/kg
per day (range = 0.36 to 12.12). The duration of propranolol inpa-
tient treatment days varied, mean days 26.5 – 19.8.
Statistical analyses
The project coordinator and statistician managed the data, and
SAS statistical software (SAS Institute) was used for analyses of the
data. Demographics were summarized by means and standard de-
viations, counts, and percentages. Differences between children in
the propranolol and nonpropranolol groups were estimated by Chi-
square tests. A 95% level of confidence was assumed.
Results
From the 380 eligible participants, 202 children participated in
the study with a participation rate of 53%. Eleven children expired,
14 were younger than the age of 5 at the time of study enrollment, 2
refused to participate, and 3 did not show up for their scheduled
clinic appointments. We were unable to contact 148 children be-
cause we did not have their updated contact information. Some of
the participants were lost to follow-up after temporary closure of
the hospital from Hurricane Ike in 2008. We are not aware of any
systematic differences between children who participated and those
we were unable to contact. The acute propranolol and non-
propranolol groups were comparable in regards to age at time of
burn, age at the time of recruitment, number of years postburn, burn
size, and days treated after the burn injury. No significant differ-
ences were found between the groups ( p < 0.05).
Of the 202 children, 89 had been randomized to the acute pro-
pranolol group and 113 in the nonpropranolol controls. More males
(n = 135, 67%) than females (n = 67, 33%) participated in the study.
Ethnicity included 187 (93%) Hispanic, 8 (4%) Caucasian, and 7
(3%) African American children. The majority of children were from
Mexico because of a Mexican Foundation that sponsors and
 120 ROSENBERG ET AL.

Table 1. Demographics for the Propranolol Table 3. Number of Children With and Without
and Nonpropranolol Groups (N = 202) Posttraumatic Stress Disorder When Pain
and Anxiety Medications Were Controlled
Propranolol* Nonpropranolol*
(n = 89) (n = 113) Propranolol* Nonpropranolol*
(n = 86) (n = 111)
Gender, n (%)
Males 62 (70) 73 (65) PTSD No PTSD PTSD No PTSD p
Females 27 (30) 40 (35)
Received pain meds
Ethnicity, n (%)
£9 days 0 7 2 17 0.38
Hispanic 81 (91) 106 (94)
‡10 days 3 76 6 86 0.43
Caucasian 2 (2) 6 (5)
African American 6 (7) 1 (1) Received anxiolytics
£9 days 0 7 3 19 0.31
Type burn, n (%)
‡10 days 3 76 5 84 0.58
Flame 70 (79) 79 (70)
Scald 10 (11) 22 (19) *Chi-square test, not significant p-value ‡0.05.
Electrical 9 (10) 12 (11) PTSD, posttraumatic stress disorder.
Mean age at time burn 7.2 – 4.7 7.4 – 4.5
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Mean years postburn 5.6 – 2.5 6.2 – 2.3

Mean age at recruitment 12.8 – 4.4 13.6 – 4.7
Mean TBSA 56.2 – 15.4 56.5 – 14.9
Mean days at admission 5.6 – 9.5 5.0 – 7.7
*Chi-square test, not significant p-value ‡0.05.
TBSA, total body surface area burned.
transports children with large burns to receive medical care at this
pediatric burn center. The etiology of burns included flame (n = 149,
74%), scald (n = 32, 16%), and electrical (n = 21, 10%) injuries. The
mean age at the time of burn was 7.3 – 4.6 years of age, mean age at
the time of study recruitment was 13.2 – 4.6 years of age, and mean
years postburn was 5.9 – 2.4. The average total body surface area
burned was 56.4% – 15.1 (range = 24%–99%). The average number
of days from the date of the burn injury to admission at this pediatric
burn center was 5.3 – 8.5 days. Additional demographic information
for the propranolol and controls is presented in Table 1.
Of 202 children, 197 children completed the MAGIC (propranolol
n = 86, nonpropranolol n = 111). Chi-square tests examined the
prevalence of lifetime PTSD at follow-up. Three (3.5%) children
treated with acute propranolol and 8 (7.2%) in the nonpropranolol
group met diagnostic criteria for PTSD in their lifetime. No between-
group difference was detected (Chi-square = 1.27, p = 0.26). It would
require at least 579 children in each group to detect a significant
difference to have a power of 0.80. Children with PTSD had smaller
burns with an average burn size of 47.4%. The average burn size
for children with PTSD in the propranolol group was 44% and for
controls it was 48.6%. Therefore, burn size is not a significant de-
terminant of PTSD.
We examined the number of children who experienced PTSD
symptoms without meeting diagnostic criteria. Thirteen (15.1%)
children who received acute propranolol and 17 (15.3%) controls
reported experiencing at least one symptom in each of the categories
Table 2. Number of Children Who Met Diagnostic
Criteria for Posttraumatic Stress Disorder
or Posttraumatic Stress Disorder Symptoms
Propranolol* Nonpropranolol*
(n = 86) (n = 111)
PTSD, n (%) 3 (3.5) 8 (7.2)
PTSD symptoms, n (%) 13 (15.1) 17 (15.3)
*Chi-square test, not significant p-value ‡0.05.
PTSD, posttraumatic stress disorder.
reexperiencing, avoidance, and increased arousal. No significant
difference was found between the groups (Chi-square = 0.00,
p = 0.97). Information regarding the rate of PTSD and PTSD
symptoms for both groups is available in Table 2.
At this pediatric burn hospital, the standard of care includes
aggressive pain and anxiety management (Ratcliff et al. 2006).
Children recovering from burns receive pain medications and an-
xiolytics, and some require antidepressants during their acute
hospital stay. Per the pain protocol, the following medications were
used on the inpatient unit: morphine and fentanyl for pain man-
agement, lorazepam for anxiety management, and fluoxetine or
imipramine for ASD and depression. Additional Chi-square ana-
lyses were done while controlling for the effects of these medica-
tions overall in children who received medications for £9 days and
‡10 days. No significant differences in the rates of PTSD were
found between the propranolol and control groups when we con-
trolled for these medications overall ( p £ 0.05). Additional infor-
mation regarding pain and anxiety medications is presented in
Table 3.
Anxiety and depression often co-occur with PTSD (Donnelly
2003; Stoddard et al. 2011). Anxiety was examined with the
RCMAS. Twelve (14%) participants in the propranolol group and
18 (17%) controls met diagnostic criteria for anxiety with total
anxiety scores greater than a T-score of 60. However, no significant
difference was found between the groups (Chi-square = 0.31,
p = 0.58). Similarly, 12 (15%) of the children who received pro-
pranolol and 15 (15%) in the nonpropranolol group met diagnostic
criteria for depression on the CDI (T-score >56) or BDI-II (raw
score >20) but differences were not significant (Chi-square = 0.00,
p = 0.99).
Discussion
Results of this study revealed that there was no statistically
significant difference in the prevalence of lifetime PTSD for chil-
dren previously treated with acute propranolol (3.5%) and children
in the nonpropranolol group (7.2%). These results are similar to the
literature on adults that explored the benefits of propranolol for the
prevention of PTSD (Pitman et al. 2002; McGhee et al. 2009; Hoge
p et al. 2012).
The literature suggests that the timing of propranolol adminis-
0.26 tration is important. The hypothesized action of propranolol is the
0.97
prevention of consolidation of traumatic memories and is, there-
fore, potentially dependent on when it is administered after a
trauma (Cahill et al. 1994; Pitman et al. 2002; Pomerantz 2006;
 PROPRANOLOL TREATMENT FOR PTSD IN CHILDREN
McGhee et al. 2009). In this study, the average time of admission to
this pediatric burn hospital was 5 – 8 days after the burn incident
and propranolol was administered within 48–72 hours of admission.
Cahill et al. (1994) examined the effects of propranolol admin-
istered 1 hour before exposure of emotional or neutral storylines.
Participants given propranolol recalled less emotional information
in comparison to controls. In a study by Pitman et al. (2002),
propranolol was administered within 6 hours of the trauma. There
was no significant difference in the rate of PTSD between the
propranolol and placebo groups, but participants in the propran-
olol group showed improvements on physiologic measures 3
months posttrauma. In a recent review, Pitman et al. (2012) ad-
dressed the importance of considering psychophysiological as-
pects of PTSD such as heart rate and skin conductance. Similarly,
Hoge et al. (2012) reported that adults who received propranolol
4–12 hours after the trauma showed improvements in physio-
logical reactivity and heart rate at follow-up.
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In a pediatric study, Nugent et al. (2010) began propranolol
treatment within 12 hours of the traumatic incident. The authors
found a gender difference that was not statistically significant.
Males treated with propranolol experienced less PTSD symptoms
at follow-up. It may be that the effect of propranolol in reducing the
risk for PTSD is dependent on how soon it is given after the trauma.
Additional research that investigates the timing and adherence to
the propranolol treatment regimen may be beneficial.
At this pediatric burn center, the rates of ASD and PTSD in
children have been relatively low. It can be speculated that early
and ongoing implementation of the pain protocol and psychother-
apy that children receive may contribute to the low prevalence of
trauma symptoms at this center. Children in the PICU receive
opiates and benzodiazepines (Ratcliff et al. 2006). The prevalence
of ASD decreased from 12% to 9% when pain was appropriately
managed (Ratcliff et al. 2006). In a recent study, which examined
lifetime PTSD in pediatric burn survivors previously treated for
ASD symptoms during their initial hospital stay and a non-ASD-
matched control group, the prevalence of PTSD in the ASD group
was 8% and in the non-ASD group it was 5% (Rosenberg et al. 2015).
Pediatric studies determined that pain is a predictor for devel-
oping trauma symptoms (Saxe et al. 2005a; Stoddard et al. 2006),
and insufficient pain management may result in PTSD for children
with burns (Saxe et al. 2001, 2005b). Saxe et al. (2001) investigated
the relationship between acute morphine given for pain manage-
ment and PTSD in pediatric burn survivors. They concluded that
children treated with higher doses of morphine during their initial
hospital stay experienced a reduction in PTSD symptoms 6 months
postburn (Saxe et al. 2001). Likewise, Stoddard et al. (2009) ex-
amined the relationship between acute morphine and PTSD for
children ages four and younger who had burn injuries. They re-
ported a significant association between morphine dose and de-
crease of arousal symptoms at 3 and 6 months postinjury.
In a multicenter study done at four pediatric burn centers,
Sheridan et al. (2014) explored the relationship between morphine
doses administered the first week of hospitalization and PTSD
symptoms. Recovery curves revealed that increased morphine do-
ses were related to the decline of PSTD symptoms in children and
the benefits lasted 4 years postburn. Holbrook et al. (2010) reported
that there was a significant relationship between morphine used for
resuscitation of adult combat veterans and the probability of de-
veloping PTSD posttrauma. In this study, there was no significant
difference in the prevalence of lifetime PTSD between the pro-
pranolol and nonpropranolol groups when pain, anxiolytics, and
antidepressants were controlled.
121
Studies on the benefits of propranolol for the management of
anxiety disorders have found mixed results. Some research reported
that propranolol may have short-term benefits for anxiety symp-
toms (Easton and Sherman 1976; Kathol et al. 1980; Peet and Ali
1986), which often occur in individuals recovering from burns. Peet
and Ali (1986) conducted a double-blind study and examined the
efficacy of propranolol, atenolol, and placebo treatment for indi-
viduals who were experiencing generalized anxiety and on a
waiting list for psychotherapy. Participants who received pro-
pranolol or atenolol reported significant improvements in anxiety
symptoms at 3 weeks, but a significant drug effect was not detected.
The medication groups also had improvements in pulse rate.
Steenen et al. (2016) did a meta-analysis of the literature on the
efficacy of propranolol for the treatment of anxiety disorders and
found inconclusive results. In this study, no significant differences
were found in the prevalence of anxiety and depression between the
groups. Propranolol may not have provided any significant reduc-
tion of anxiety or depression because all of the pediatric burn
survivors received intense medication management and psycho-
therapy as part of the recovery process.
Limitations
The prevalence of lifetime PTSD may be lower than anticipated
because some children sustained burn injuries before they were 5
years of age and were very young to recall events related to their
injury (n = 46 propranolol, n = 56 nonpropranolol). Results might
have been different if participants were injured when they were
school-aged. In this population of children, the triggers for PTSD
are the burn incident as well as the prolonged treatment, including
wound care and debridement over many days. By the time the
subjects reached the burn hospital, some of the triggers for PTSD
might have been missed.
Another limitation is that a cohort of children was assessed at
one time point instead of multiple times. Similar studies that ex-
amined the prevalence of trauma symptoms have assessed indi-
viduals at multiple times postinjury. Follow-up evaluations at 6
months, 1, 2, 5, and 10 years postburn may provide valuable in-
formation that was not obtained and, in turn, have important
treatment implications.
It is possible that the difference in the prevalence of PTSD in the
groups may have been obscured by use of aggressive pain and
anxiety management on the inpatient unit. A greater difference
might have been evident otherwise. In this study, we controlled for
the effects of pain, anxiety, and antidepressants as a whole without
controlling for each specific medication administered. Research has
found that there is a relationship between morphine dose and PTSD
at follow-up. Future research examining the effects of specific
medications would be informative.
Another limitation is that severity of PTSD was not examined
because of the small number of children who met diagnostic criteria
for lifetime PTSD (n = 3 propranolol, n = 8 controls). Also, there
was no control group that did not have burn injuries. In addition, the
results of this study may not generalize to other pediatric groups.
The sample consisted of a large number of children from Mexico
that may not be representative of other burn centers.
Conclusion
The benefits of propranolol for preventing PTSD in pediatric
burn survivors has not been thoroughly explored. In this study,
there was no significant difference in the prevalence of PTSD in
children with major burns who received acute propranolol and
 122
nonpropranolol controls. Additional research investigating the
long-term benefits of propranolol in the prevention of trauma
symptoms with assessment at multiple time points is warranted.
Clinical Significance
This is the first study that examined whether acute propranolol
prevented the development of lifetime PTSD and comorbid anxiety
and depression in pediatric burn survivors with major burn injuries.
There is limited pharmacological research on the prevention of
major psychiatric disorders in pediatrics. The benefits of propran-
olol treatment for the prevention of these psychiatric disorders have
not been well demonstrated, but additional research is warranted to
determine the efficacy of this medication in preventing major
psychiatric disorders in traumatized children.
Acknowledgments
Downloaded by Tufts University package NERL from www.liebertpub.com at 03/17/18. For personal use only.
This research was supported by a Shrine Grant 71000. The
contents of this article were partially supported by a grant from
the National Institute on Disability, Independent Living, and Re-
habilitation Research (NIDILRR H133A970019, H133A020102,
H133A070026). The current NIDILRR grant number is
90DPBU0003. NIDILRR is a Center within the Administration for
Community Living (ACL), Department of Health and Human Ser-
vices (HHS). The contents of this article do not necessarily represent
the policy of NIDILRR, ACL, or HHS, and you should not assume
endorsement by the federal government. The authors would like to
thank the children and families who participated in this study.
Disclosures
No competing financial interests exist.
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Address correspondence to:
Laura Rosenberg, PhD
Shriners Hospitals for Children-Galveston
815 Market Street
Galveston, TX 77550
E-mail: lrosenbe@utmb.edu