Does Acute Propranolol Treatment Prevent Posttraumatic Stress Disorder,Anxiety,and Depression in Children with Burns?

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 antidepressants 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.

Introduction

The 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 Edition or DSM-5; American Psychiatric Association 2013). Clinical experience suggests that PTSD in pediatric burn survivors may result 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 investigated 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 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 responded favorably to these medications (Robert et al. 2008).

Recently, research has focused on approaches to prevent the development 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. Children in the sertraline and placebo groups experienced less trauma symptoms 6 months postburn as measured by The Diagnostic Interview for Children and Adolescents (DICA); however, the difference 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 β-adrenergic antagonist blocker, in preventing PTSD after a traumatic 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 randomized 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).

The purpose of this study was to examine whether acute propranolol 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 anticipated 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 hospitalization 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, individuals 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 symptoms 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 Association 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 disorders in children and adolescents. The format is comparable to the DICA (Reich 2000; Reich and Todd 2002).

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 developed 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 children 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 indicating higher levels of anxiety. The total anxiety score has a mean 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 Depression Inventory (CDI) is a 27-item self-report, gender normed measure 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, ineffectiveness, 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 Inventory (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/caregiver, 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 completed 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 questions, clarification was provided by the person conducting the clinical 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 records, 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 psychologists 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 inpatient 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 deviations, 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 because 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 nonpropranolol 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 differences were found between the groups (p < 0.05).

Of the 202 children, 89 had been randomized to the acute propranolol 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 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.

Table 1.

Demographics for the Propranolol and Nonpropranolol Groups (N = 202)

	Propranolol^ (*n = 89)	Nonpropranolol^ (*n = 113)
Gender, n (%)
Males	62 (70)	73 (65)
Females	27 (30)	40 (35)
Ethnicity, n (%)
Hispanic	81 (91)	106 (94)
Caucasian	2 (2)	6 (5)
African American	6 (7)	1 (1)
Type burn, n (%)
Flame	70 (79)	79 (70)
Scald	10 (11)	22 (19)
Electrical	9 (10)	12 (11)
Mean age at time burn	7.2 ± 4.7	7.4 ± 4.5
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.

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 determinant 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 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.

Table 2.

Number of Children Who Met Diagnostic Criteria for Posttraumatic Stress Disorder or Posttraumatic Stress Disorder Symptoms

	Propranolol^ (*n = 86)	Nonpropranolol^ (*n = 111)	p
PTSD, n (%)	3 (3.5)	8 (7.2)	0.26
PTSD symptoms, n (%)	13 (15.1)	17 (15.3)	0.97

Chi-square test, not significant p-value ≥0.05.

PTSD, posttraumatic stress disorder.

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 anxiolytics, 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 management, lorazepam for anxiety management, and fluoxetine or imipramine for ASD and depression. Additional Chi-square analyses were done while controlling for the effects of these medications 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 controlled for these medications overall (p ≤ 0.05). Additional information regarding pain and anxiety medications is presented in Table 3.

Table 3.

Number of Children With and Without Posttraumatic Stress Disorder When Pain and Anxiety Medications Were Controlled

	Propranolol^ (*n = 86)		Nonpropranolol^ (*n = 111)
	PTSD	No PTSD	PTSD	No PTSD	p
Received pain meds
≤9 days	0	7	2	17	0.38
≥10 days	3	76	6	86	0.43
Received anxiolytics
≤9 days	0	7	3	19	0.31
≥10 days	3	76	5	84	0.58

Chi-square test, not significant p-value ≥0.05.

PTSD, posttraumatic stress disorder.

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 propranolol 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 children 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 et al. 2012).

The literature suggests that the timing of propranolol administration is important. The hypothesized action of propranolol is the prevention of consolidation of traumatic memories and is, therefore, potentially dependent on when it is administered after a trauma (Cahill et al. 1994; Pitman et al. 2002; Pomerantz 2006; 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 administered 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 propranolol group showed improvements on physiologic measures 3 months posttrauma. In a recent review, Pitman et al. (2012) addressed the importance of considering psychophysiological aspects 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 physiological reactivity and heart rate at follow-up.

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 psychotherapy 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 developing 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 management 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) examined the relationship between acute morphine and PTSD for children ages four and younger who had burn injuries. They reported a significant association between morphine dose and decrease 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 doses 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 developing PTSD posttrauma. In this study, there was no significant difference in the prevalence of lifetime PTSD between the propranolol and nonpropranolol groups when pain, anxiolytics, and antidepressants were controlled.

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 symptoms (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 individuals who were experiencing generalized anxiety and on a waiting list for psychotherapy. Participants who received propranolol 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 reduction of anxiety or depression because all of the pediatric burn survivors received intense medication management and psychotherapy 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 examined the prevalence of trauma symptoms have assessed individuals at multiple times postinjury. Follow-up evaluations at 6 months, 1, 2, 5, and 10 years postburn may provide valuable information 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 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 propranolol 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.

Footnotes

Acknowledgments

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 Rehabilitation 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 Services (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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