As Chief of Staff at the Shriners Hospital for Children (SHC) – Galveston, you are involved in the treatment and rehabilitation of severe burns patients. How did you become active in this area of medicine?

I first became involved while working for the military at the Institute of Surgical Research in San Antonio in the early 1970s. During this time, I came into contact with many victims of military burn injuries, many of whom had poor outcomes in life. I was involved as a scientist in treating burn injuries and studying the metabolic responses to injury and treatment. This became a goal of my life’s work.

Can you give an overview of the demographics of the patients which are treated at SHC – Galveston and the facilities offered by the unit?

We have a paediatric burn hospital which currently treats 2,000 active paediatric burn patients from around the world. SHC – Galveston is a 30-bed hospital with an average intensive care unit (ICU) census of 10 in-patients per day. We also treat over 100 patients with burns affecting more than 30 per cent of the total body surface area. The Blocker Burn unit – one of the first burn hospitals built in the US – is a six-bed burn ICU. It was set up largely in response to a disaster when a mononitrate-containing ship exploded in Texas City in 1947, leaving 3,000 injured individuals who were treated by a highly skilled plastic surgeon named Truman Blocker of the University of Texas Medical Branch (UTMB) at Galveston. Both centres at SHC – Galveston and UTMB are certified as burn centres by the American Burn Association and American College of Surgeons.

What kind of therapies can help post-trauma burn victims? Is treatment tailored to individual patients’ needs?

The physical effects of burns can continue for more than two years after the injury;

children may stop growing and patients are rendered weak. Post-acute-burn care treatment centres on exercise, giving agents to improve strength and muscle, as well as decrease anxiety and treat pain. Patients develop an intense itch over the first year post-injury, so treatment of this symptom is extremely important. People with burns over 40 per cent of their total body surface usually receive five operative interventions during their acute hospital stay and seven reconstructive operations over the subsequent eight to 10 years. Primary treatments aim to decrease scarring and improve range of motion.

What characterises a hypermetabolic response?

The hypermetabolic response is characterised by tachycardia – an increase in resting energy expenditure, prolonged protein catabolism and loss of bone mineral content, which leads to brittle bones.

In what capacity does treatment and care differ in paediatric burns patients? Is the hypermetabolic response more common in children?

In children, growth is stunted by the burn injuries. Hypermetabolic and hypercatabolic children need more strengthening exercises as well as greater range of motion exercise.

You have recently been involved with pioneering research into the use of propranolol to reduce muscle wasting in burns victims. Can you give a synopsis of the research performed?

We found that giving propranolol for a year post-injury can decrease the fight or flight response driven by catecholamines, decrease tachycardia, improve bone mineral content and gradually improve physical function.

The cohort given propranolol for a year post-injury improved significantly, displaying decreased heart rate and blood pressure, and improved lean body mass accretion.

Will it be possible to translate this breakthrough to the clinical setting? If so, what will be the associated implications?

We believe that control of the stress response by specific pharmacologic agents may decrease after any kind of injury, not just burns. It may improve the conditions of patients in all stress-related phenomena.

Finally, rehabilitation is an important aspect of the aftercare of patients in this context, what kind of programmes are undertaken to enable recovery?

The most important new rehabilitation recommendations consist of propranolol use for the first year post-burn, and patient aerobic exercise at moderate to high intensities, five times a week, including progressive resistance training with loads that are lifted for eight to 15 repetitions, two to three sets, three times per week.

The physical and psychological trauma affecting severe burns patients can persist years after an incident. Professor David N Herndon is studying the potential of propranolol treatments to mitigate the long-term effects of severe burn injuries

On the mend

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SEVERE BURNS CAUSE significant metabolic changes that affect patients long after their injury. Sufferers commonly experience chronically elevated heart rate (tachycardia) and an increased breakdown of proteins – known as protein catabolism – for more than two years following the incident. Catabolism leads to a decrease in the patient’s muscle mass and an increased risk of organ failure. Brittle bones can also result post-burn, increasing the chances of breakage. In children with severe burns this can also lead to stunted growth. Moreover, patients often experience associated psychological disorders in the form of post-traumatic stress disorder, acute stress disorder and anxiety.

Increased heart rate is a long-term effect caused by the release of catecholamines, and typically occurs as a response to stress as part of the protective fight or flight mechanism. This process is triggered by the external environment and is normally a short-term response. However, in severe burns patients, catecholamines are found in elevated levels up to two years after the incident, resulting in long-term increased heart rate, which can lead to further negative side-effects. Amongst other conditions, elevated levels of catecholamines are associated with cardiotoxicity.

Professor David N Herndon of the University of Texas Medical Branch is Chief of Staff at the Shriners Hospital for Children (SHC) – Galveston. He is currently investigating the effects of prolonged propranolol treatment on children and adults who have suffered extensive body area burns. Propranolol is an antagonist to these receptors (named beta-adrenergic receptors) with capacity to reduce catecholamine signals and by extension heart rate of burn patients. Herndon seeks to tackle longer term symptoms in paediatric and adult patients by blocking the catecholamines receptors, thereby mitigating their effects (eg. reducing heart rate).

A NOVEL FORM OF TREATMENT

Beta blockers (drugs of the same family as propranolol) are already used to treat patients following major surgical procedures and have been found to reduce cardiac complications and mortality rates. Although propranolol is mainly used to treat the physical symptoms of anxiety, Herndon believes that the drug may represent a solution to both physical and psychological trauma. This novel hypothesis

could provide an important pathway for a more holistic approach to burn treatment.

Herndon’s study was conducted using a group of 179 paediatric patients with more than 30 per cent total body surface area burns. Half the patients received 4 mg/kg of propranolol daily whilst the other half served as a control group. Heart rate and blood pressure were recorded four times a day, while measurements of resting energy expenditure, cardiac function and body composition were made every three months for a year.

EFFECTS OF PROPRANOLOL TREATMENT ON CHILDREN

The results of this study show that the year-long administration of propranolol to paediatric patients significantly reduced the predicted heart rate and resting energy of the patients compared to those who did not receive the drug. The group receiving propranolol experienced a change in body composition in the form of a decrease in the accumulation of central fat mass.

Propranolol was also shown to slow mineral loss in the bones of patients. Mineral content of bones is linked to their strength, showing propranolol to be effective in counteracting bone weakness typically found in burn patients.

While the longer term physical effects of burns have obviously been reduced, demonstrating propranolol’s benefits on the minds of patients has proven more challenging. The initial study shows no effect on acute stress disorder or post-traumatic stress disorder in patients given short- or long-term propranolol treatment. In order to determine whether propranolol impacts psychological outcomes of severe burns victims, studies using larger numbers of

patients that include a follow-up over longer time periods represent a promising area for future studies.

A further consideration when assessing this approach for clinical use is that care must be taken when administering propranolol as there are risks associated with its use. For example, the lower heart rate propranolol induces can lead to a decrease in the blood flow to other organs and has been shown to cause severe bronchospasm in some patients.

FUTURE DIRECTIONS

The general results of this research may benefit a wide variety of patients who have a negative nitrogen balance, such as those with trauma or those who are undergoing general surgery. Herndon explains that further investigations need to be carried out in order to further the use of propranolol to treat burn victims: “We need to discover whether propranolol can be equally effective in adults as it was in children and to find the mechanisms of actions in order that more specific drugs can be developed”.

Current research suggests that long-term benefits (growth, cardiac health and improvement in the metabolic syndrome) can be more effectively quantified using a larger population study. Further study of the long-term outcomes for patients is also planned, namely an evaluation of anxiety, acute distress disorder and post-traumatic stress disorder.

COLLABORATION AND THE FUTURE

In the pursuit of holistic treatment for burns victims, it is worth noting that Herndon’s work has not been conducted in isolation. As Chief of Staff at SHC – Galveston, he has the opportunity to incorporate other research studies into his proposals. Most notably, Professor Oscar E Suman (see p36) directs a wellness and exercise centre for burned children, which is part of a burn centre grant. This comprises a 12-week structured and supervised exercise programme and goes far beyond the written set of instructions for physical and occupational therapy activities at home that usually constitute patient aftercare.

Herndon’s work has shown propranolol to be effective in treating many of the physical symptoms affecting post-burn paediatric patients. However, he has also raised awareness of the importance of looking beyond

Reducing burn traumaCurrent medical research at the University of Texas Medical Branch at Galveston is investigating the use of propranolol as a treatment for extensive burns. Initial studies on children have shown encouraging results, with reduced incidence of problems including chronically elevated heart rate and bone weakness

The general results of this research

may benefit a wide variety of

patients who have a negative

nitrogen balance, such as those

with trauma or those who are

undergoing general surgery

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40 INTERNATIONAL INNOVATION

short-term physical after-effects of severe burn injuries. Patients need to be studied well into adulthood to determine whether these prolonged episodes of tachycardia and increased cardiac work have long-term effects on cardiovascular morbidity. Moreover, it must be established whether decreasing heart rate with propranolol reduces this morbidity.

Analysis of long-term administration of propranolol in children with major burns indicates that Herndon’s approach to treatment is safe and markedly decreases

heart rate and cardiac work. Analysis also shows that this treatment decreases central body mass, reduces truncal fat, and improves lean body mass and bone mineral density. Ultimately, Herndon’s work suggests that a larger study population will show long-term health benefits in terms of growth, cardiac health and improvement of the metabolic syndrome. If this can be conclusively established and propranolol prescribed more widely in clinical settings, the wellbeing of burn sufferers everywhere could be significantly improved.

THE USE OF PROPRANOLOL IN BURNS

OBJECTIVES

To determine the safety and efficacy of propranolol given for one year on cardiac function, resting energy expenditure and body composition in a prospective, randomised, single-centre, controlled study in (paediatric and adult) patients with extensive burns.

PARTNERS

Oscar E Suman, PhD • Deb A Benjamin, MSN • Celeste C Finnerty, PhD • Kristofer Jennings, PhD • Makiko Kobayashi, PhD • Jong Lee, MD • Bruce A Luxon, PhD • Walter J Meyer, III, MD • Ronald P Mlcak, PhD • Labros Sidossis, PhD • Fujio Suzuki, PhD • Csaba Szabo, MD, PhD

FUNDING

National Institutes of Health: P50 GM060388, R01 HD049471, R01 GM056687 • National Institute on Disability and Rehabilitation Research: H133A120091, H133A070026 • Shriners Hospital for Children: 71009, 71008, 71006, 79141, 84080 • American Burn Association/Department of Defense: W81XWH-09-2-0194, W81xwh-11-1-0835

CONTACT

Professor David N Herndon, MD, FACS Chief of Staff

Shriners Hospital for Children – Galveston 815 Market Street Galveston TX 77550 USA

T +1 409 770 6744 E dherndon@utmb.edu

DAVID N HERNDON, MD is Chief of Staff at Shriners Hospital for Children – Galveston, Professor of both the Department of Surgery and Department of Pediatrics at the University of Texas Medical Branch at Galveston and the Jesse H Jones Distinguished Chair in Burn Surgery.

INTELLIGENCE

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