Effects of Propranolol and Exercise Training in Children with Severe Burns

doi:10.1016/j.jpeds.2012.09.015

The Journal of Pediatrics

Volume 162, Issue 4, April 2013, Pages 799-803.e1

https://doi.org/10.1016/j.jpeds.2012.09.015 Get rights and content

Objectives

To investigate whether propranolol administration blocks the benefits induced by exercise training in severely burned children.

Study design

Children aged 7-18 years (n = 58) with burns covering ≥30% of the total body surface area were enrolled in this randomized trial during their acute hospital admission. Twenty-seven patients were randomized to receive propranolol, whereas 31 served as untreated controls. Both groups participated in 12 weeks of in-hospital resistance and aerobic exercise training. Muscle strength, lean body mass, and peak oxygen consumption (VO₂ peak) were measured before and after exercise training. Paired and unpaired Student t tests were used for within and between group comparisons, and χ² tests for nominal data.

Results

Age, length of hospitalization, and total body surface area burned were similar between groups. In both groups, muscle strength, lean body mass, and VO₂ peak were significantly greater after exercise training than at baseline. The percent change in VO₂ peak was significantly greater in the propranolol group than in the control group (P < .05).

Conclusions

Exercise-induced enhancements in muscle mass, strength, and VO₂ peak are not impaired by propranolol. Moreover, propranolol improves the aerobic response to exercise in massively burned children.

Section snippets

Methods

From January 2000-May 2011, 246 children were enrolled in a double-blinded trial during acute admission to Shriners Hospitals for Children (Galveston, Texas). Inclusion criteria were age 7-18 years, electrical or flame burns covering ≥30% of the total body surface area (TBSA), and participation in the exercise program within 6 months post-burn. Exclusion criteria included receipt of study drugs other than propranolol, and presence of psychological disorders, quadriplegia, or certain behavior or

Results

Between January 2000 and May 2011, 62 children were enrolled in this study and randomized to the PROPEX group or EX group, with both groups participating in the exercise program. Twenty-seven PROPEX patients were compared with 31 EX controls. Nine patients (EX = 4 and PROPEX = 5) could not complete the 12 weeks of exercise and discontinued exercise training for reasons such as immigration status, parents needing to take care of other family members back home, and the aftermath of Hurricane Ike.

Discussion

This study demonstrates that exercise training in combination with propranolol improves the physical function of burned children during the rehabilitation process. After completion of 12 weeks of exercise training, all children exhibited a 50% increase in muscle strength, an outcome that has been previously reported in other pediatric patient populations.21, 22, 23, 24, 25, 26, 27, 28, 29 Further, strength gains observed in children in the control group were no different from those of children

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Cited by (42)

The efficacy of resistance training in addition to usual care for adults with acute burn injury: A randomised controlled trial
2021, Burns
Resistance training immediately after a burn injury has not been investigated previously. This randomised, controlled trial assessed the impact of resistance training on quality of life plus a number of physical, functional and safety outcomes in adults with a burn injury.
Patients were randomly assigned to receive, in addition to standard physiotherapy, four weeks of high intensity resistance training (RTG) or sham resistance training (CG) three days per week, commenced within 72 h of the burn injury. Outcome data was collected at six weeks, three and six months after burn injury. Quality of life at 6 months was the primary endpoint. Data analysis was an available cases analysis with no data imputed. Regression analyses were used for all longitudinal outcome data and between-group comparisons were used for descriptive analyses.
Forty-eight patients were randomised resistance training (RTG) (n = 23) or control group (CG) (n = 25). The RTG demonstrated improved outcomes for the functional domain of the Burn Specific Health Scale-Brief (p = 0.017) and the Quick Disability of Arm Shoulder and Hand (p < 0.001). Between group differences were seen for C-reactive protein and retinol binding protein (p = 0.001). Total quality of life scores, lower limb disability, muscle strength and volume were not seen to be different between groups (p > 0.05).
Resistance training in addition to usual rehabilitation therapy showed evidence of improving functional outcomes, particularly in upper limb burn injuries. Additionally, resistance training commenced acutely after a burn injury was not seen to be harmful to patients.
Anabolic and anticatabolic agents used in burn care: What is known and what is yet to be learned
2020, Burns
Citation Excerpt :
Porro et al. demonstrated, in a study on children with burns greater than 30% of the total body surface area (TBSA > 30%), that propranolol increases the improvement in cardiopulmonary fitness during the rehabilitation phase. Moreover, Rivas et al. recently showed that treatment with propranolol does not interfere in exercise thermoregulation in children who experienced severe burns [24,25]. The effects of propranolol have also been demonstrated on molecular and cellular levels.
Major thermal injury induces profound metabolic derangements secondary to an inflammatory “stress-induced” hormonal environment. Several pharmacological interventions have been tested in an effort to halt the hypermetabolic response to severe burns. Insulin, insulin growth factor 1, insulin growth factor binding protein 3, metformin, human growth hormone, thyroid hormones, testosterone, oxandrolone, and propranolol, among others, have been proposed to have anabolic or anticatabolic effects. The aim of this broad analysis of pharmacological interventions was to raise awareness of treatment options and to help establishing directions for future clinical research efforts. A PubMed search was conducted on the anabolic and anticatabolic agents used in burn care. One hundred and thirty-five human studies published between 1999 and 2017 were included in this review. The pharmacological properties, rationale for the treatments, efficacy considerations and side effect profiles are summarized in the article. Many of the drugs tested for investigational purposes in the severely thermally injured are not yet gold-standard therapies in spite of their potential benefit. Propranolol and oxandrolone have shown great promise but further evidence is still needed to clarify their potential use for anabolic and anticatabolic purposes.
Effects of Community-Based Exercise in Adults With Severe Burns: A Randomized Controlled Trial
2020, Archives of Physical Medicine and Rehabilitation
To investigate the efficacy of community-based exercise programs in the rehabilitation of adult patients with burns compared with standard of care (SOC).
Randomized controlled trial, with 2:1 randomization.
Assessments were performed in a hospital setting. The intervention was performed in a community setting.
Adult patients (N=45) with ≥30% total body surface area burns were randomized to participate in a community-based exercise program (n=31) or SOC (n=14). Patient sampling was consecutive and referred.
The community-based exercise program consisted of 12 weeks of exercise with a community-based trainer after hospital discharge. The SOC group did not receive exercise training.
Change in lean body mass index, peak torque, and peak oxygen consumption from discharge to 12 weeks postdischarge, presented as mean ± SE.
The community-based exercise program group showed a significant increase in peak oxygen consumption compared with SOC (community-based exercise program: Δ=7.723±1.522mL/kg/min, P=.0006; SOC: Δ=2.200±1.150mL/kg/min, P=.0765; community-based exercise program vs SOC, P=.0236). The community-based exercise program group exhibited a significant within group increase in lean body mass index (Δ=1.107±0.431kg/m², P=.0003; SOC: Δ=1.323±0.873kg/m², P=.2808). Both groups showed significant within-group increases in peak torque (community-based exercise program: Δ=35.645±7.566Nm, P=.0003; SOC: Δ=34.717±11.029Nm, P=.0082). No significant differences were noted between the 2 groups for lean body mass index or peak torque.
Patients who participate in a community-based exercise program show significant improvements in cardiopulmonary fitness compared with SOC, supporting the use of a community-based exercise program as an alternative therapy to SOC in adults with severe burns.
One-Year Comparison of a Community-Based Exercise Program Versus a Day Hospital–Based Exercise Program on Quality of Life and Mental Health in Severely Burned Children
2020, Archives of Physical Medicine and Rehabilitation
To compare the effects of long-term psychosocial functioning and mental health of a “day hospital”–based exercise program (DAYEX) versus a community-based exercise program (COMBEX).
A prospective design that consisted of 2 groups (DAYEX and COMBEX).
A children's hospital specialized in burn care.
Patients (N=18; DAYEX [n=9], COMBEX [n=9]) were assessed at intensive care unit discharge and up to 1 year postburn.
The Child Health Questionnaires (CHQ–Child Form [CHQ-CF87] and CHQ–Parent Form [CHQ-PF28]) were used to assess changes in quality of life from discharge to 1 year postburn.
CHQ-PF28 and CHQ-CF87.
Demographic characteristics and total body surface area burned were similar in both groups. Length of hospital stay was significant in the COMBEX group. CHQ-CF87 and CHQ-PF28 documented significant improvements in both groups between discharge and 1 year. Significance was evident in Physical Functioning, Bodily Pain, Self-Esteem, Change in Health, and Family Activities. CHQ-CF87 showed improvement in Family Cohesion in COMBEX more than DAYEX. CHQ-PF28 showed improvement in Role/Social Limitations–Emotional, Bodily Pain, and Family Activities in COMBEX more than DAYEX.
The proposed COMBEX program is feasible and beneficial physically, psychosocially, and mentally. The results show some improvements in the COMBEX group in optimizing function and health in severely burned children. The COMBEX group performed at least as well as the DAYEX group. Larger-scale studies are needed to validate current findings.
Relationship between lean body mass and isokinetic peak torque of knee extensors and flexors in severely burned children
2019, Burns
Citation Excerpt :
The training consisted of resistance and aerobic exercise up to 5 days per week and began immediately after discharge from the intensive care unit [8]. Cardiorespiratory capacity as well as muscle strength and lean body mass (LBM) can be improved after structured exercise programs [7,9,10]. Muscle mass is a major contributor to the body’s total LBM.
Severe burns cause hypermetabolic responses and prolonged hospitalization, resulting in loss of body mass and muscle strength. This study aimed to determine whether long-term gains in lean body mass (LBM) after structured exercise programs are functionally meaningful and related to greater muscle strength in severely burned children.
LBM and muscle strength were measured at discharge and at 6, 12, 24, and 36 months after burn in 349 children. Body composition, including LBM, was measured via dual-emission X-ray-absorptiometry. Peak torque was measured using Biodex dynamometer at varying angular velocities (90, 120, 150, 180°/s). Pearson correlation analysis evaluated the association between LBM and peak torque.
LBM progressively increased from discharge (32.5 ± 11.5 kg) to 36 months following injury (40.2 ± 12.3 kg). Peak torque and peak torque/LBM increased from discharge (56.4 ± 34.0 Nm and 1.7 ± 34.0 Nm kg⁻¹) to 36 months after burn (102.3 ± 43.8 Nm and 2.5 ± 0.7 Nm kg⁻¹, p < 0.01 for both). LBM and peak torque at all angular velocities showed moderate/strong correlations, with 120°/s being the strongest (all time-points: R² ≥ 0.57).
In severely burned children participating in a rehabilitative exercise program, gains in LBM over time are related to increases in muscle strength, suggesting that gained muscle mass is functional. Measurement of muscle strength at an angular velocity of 120°/s best reflects gains in LBM and should be considered for reliable measure of strength in future studies.
Children with severe burns display no sex differences in exercise capacity at hospital discharge or adaptation after exercise rehabilitation training
2018, Burns
Females have a 50% increased risk of death from burn injury compared to males. However, whether exercise capacity and exercise induced training adaptations differ between burned boys and girls is unknown. This project tested the hypothesis that girls with burns have lower exercise capacity and different exercise induced training adaptations.
Twenty-five girls were matched to 26 boys (mean, 95%CI; years 13 [12,14], cm 151 [143,161], kg 54 [45,63]; each P > 0.05) for burn injury (% total body surface area burn, 54 [45,62]; P = 0.82). Lean body mass (LBM), strength (peak torque) and cardiorespiratory fitness (peak VO₂) were normalized to kg LBM and compared as a percentage of age–sex matched non-burned children (n = 26 boys, years 13 [12,14]; n = 25 girls, years 13 [12,14]) at discharge (DC) and after aerobic and resistance rehabilitation exercise training (RET).
Using a 2-way factorial ANOVA (group × time), we found both groups had similar 11% change in LBM (87.3% of non-burned values [82.2,92.3]) and after the RET (92.8% [87.2,98.3]; main effect, time P < 0.0001). Peak torque increased similarly by 16% in both groups (% of age–sex matched non-burned DC, 55.9 [51.3,60.5]; after RET, 77.5 [72.1,82.9]; main effect, time P < 0.0001). Likewise, peak VO₂ increased in both groups by 15% (% of age–sex matched non-burned DC, 56.8 [52.4,61.2] to RET, 72.2 [67.6,76.8]; main effect, time; P < 0.0001). Burned children exercise at greater percentage of their peak VO₂ and peak HR compared to non-burned children (Interaction, group × time, P < 0.0001).
The burn injury does not have sex-dependent effects on LBM or exercise capacity in severely burn injured children. Differences in relative peak VO₂ and peak HR suggest the need for burn specific exercise programs for improving the efficacy of a rehabilitation program.

View all citing articles on Scopus

: Supported by the National Institute for Disability and Rehabilitation Research (H133A070026 and H133A70019), the National Institutes of Health (NIH; P50-GM60338, R01-HD049471, and T32-GM8256), and Shriners Hospitals for Children (84080 and 8760). L.P. is supported by NIH (T32-GM8256). The authors declare no conflicts of interest.

: Registered with ClinicalTrials.gov: NCT00675714.

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Original ArticleEffects of Propranolol and Exercise Training in Children with Severe Burns

Objectives

Study design

Results

Conclusions

Section snippets

Methods

Results

Discussion

Lancet

Arch Phys Med Rehabil

Burns

Resuscitation

Egyp J Med Hum Genet

Res Dev Disabil

Int J Cardiol

Surgery

Am J Cardiol

Long-term persistance of the pathophysiologic response to severe burn injury

PLoS One

Extent and magnitude of catecholamine surge in pediatric burned patients

Shock

Effect of a supervised exercise and physiotherapy program on surgical interventions in children with thermal injury

J Burn Care Rehabil

Effects of a 12-week resistance exercise program on skeletal muscle strength in children with burn injuries

J Appl Physiol

Effects of exercise training on resting energy expenditure and lean mass during pediatric burn rehabilitation

J Burn Care Res

Effect of β1-selective and nonselective β-blockade on work capacity and muscle metabolism

Clin Physiol

Factors contributing to increased muscle fatigue with β-blockers

Can J Physiol Pharmacol

The effect of acute vs chronic treatment with β-adrenoceptor blockade on exercise performance, haemodynamic, and metabolic parameters in healthy men and women

Br J Clin Pharmacol

Exercise performance and β-blockade

Sports Med

Exercise capacity, energy metabolism, and β-adrenoceptor blockade. Comparison between a β1-selective and a non-selective β blocker

Eur J Appl Physiol Occup Physiol

Energy expenditure and caloric balance after burn: increased feeding leads to fat rather than lean mass accretion

Ann Surg

ACSM's guidelines for exercise testing and prescription

Council on School Health. Active healthy living: prevention of childhood obesity through increased physical activity

Pediatrics

Original Article
Effects of Propranolol and Exercise Training in Children with Severe Burns