title: Epidemiology and outcomes of patients admitted to hospital with a burn injury in Scotland
Creators: name: McGovern, Christopher
Publisher: name: University of Glasgow
Year: 2023

description: Burn injuries are a significant cause of both morbidity and mortality throughout the world. The prevalence of burn injuries and the demographics of those affected vary across the globe, especially between developed and developing countries. However, the risk of burn injury remains consistently higher in individuals from a background of socioeconomic deprivation.

With advances in medical care in recent decades, the chances of survival following major burn injury have increased significantly. With individuals now surviving much more substantial injuries, there is an increasing appreciation of the long-lasting pathophysiological and psychological consequences that can occur following such an injury. Common sequelae include chronic pain, pruritus, depression or anxiety, post-traumatic stress disorder and an increase in the risk of cardiovascular disease, cancer and various infections.

However, the exact aetiology and risk factors associated with being more likely to suffer such detrimental consequences are incompletely understood. Additionally, the deterioration in health conditions after injury may be explained by both the risk factors common to sustaining a burn injury and the physiological impact of the burn injury itself.

The studies detailed in this thesis aim to explore the epidemiology of, and mortality from, burn injuries in Scotland; investigate the effectiveness of using neuropathic agents to manage the symptoms of burn-related pruritus; describe the prevalence and predictors of pruritus after burn injury; explore the use of a protocolised treatment regimen for pruritic symptoms; and use national administrative databases to explore the long-term consequences following survival of a burn injury including the use of drugs to manage pain and mental health conditions and the likelihood of death in the following years.

This thesis includes a systematic review and meta-analysis to explore the effectiveness of drugs commonly used to treat neuropathic pain in the management of burn-related pruritus. Although there is a paucity of evidence that exists, gabapentinoids appear to be effective at reducing pruritus severity scores by 2.96 (95% CI 1.20, 4.73) on a zero to ten scale when compared to antihistamine or placebo.

Using prospective data collected as part of a quality improvement project in a tertiary referral burn ward, this study explored the factors associated with pruritus severity in patients with a burn injury. Multivariable linear regression analysis demonstrated that increasing size of burn, as measured by surface area, flame burns, a history of smoking and history of alcohol use disorder were all associated with an increase in pruritus severity. Although low serum vitamin D levels were prevalent among this cohort of patients, with 83% of patients having serum vitamin D levels &lt;50nmol/L, the presence or severity of this apparent deficiency did not correlate with the severity of pruritic symptoms. The use of a protocolised approach to pruritus management with various antihistamine drugs and gabapentin in the presence of neuropathic features was consistently effective at reducing pruritus severity scores.

The remaining chapters of this thesis used large linked national datasets to describe the epidemiology and outcomes for patients that suffered a burn injury requiring hospital admission in Scotland. The results show that males are more likely to sustain a burn injury than females, accounting for 63% of admissions. Children were more likely to sustain a scald injury (63% of injuries) with flame burns being relatively rare in children (6%) but much more prevalent in adults (29%). Patients from areas of socioeconomic deprivation made up a greater proportion of both the adult and paediatric cohort. Children from an ethnic minority background were found to be at a higher proportion than would be expected for the general population in Scotland, a pattern not seen in the adult cohort.

Of the adult population, 2.73% died within 30 days of their burn injury. Multivariable cox proportional hazards regression analysis demonstrated that, in keeping with multiple previous studies, increasing age (HR 1.08), increasing size of burn (HR 1.12) and the presence of smoke inhalation injury (HR 14.54) were all associated with an increased mortality. Additionally, a pre-existing history of depression or neurological disorder were also independently associated with mortality (HR 13.65 and 6.48 respectively).

Pre-injury use of drugs such as opioids was significantly higher in this burn-injured cohort compared to the general population in Scotland (25.8% vs 18% respectively). Following burn injury, the use of opioids increased from 25.8% to 38.5% of patients. This increase was evident in prescriptions for both strong and weak opioids. An increase was also seen in the number of patients receiving recurrent (three or more) prescriptions. Factors associated with an increase in opioid use after injury included female gender, previous opioid use, increasing age, socioeconomic deprivation and increasing comorbidity burden.

Compared with the general population of Scotland, the pre-injury use of various drugs for mental health conditions were all higher in this burn-injured cohort including antidepressants (15.2% vs 26.6% respectively), antipsychotics (1.5% vs 6%) and anxiolytics (6.8% vs 16.3%). This study did not demonstrate a higher proportion of patients using these drugs post-injury, however, following a burn, there was a higher burden of drug utilisation, with more patients receiving multiple drugs for mental health conditions, and a higher frequency of prescriptions. Factors associated with this increase in the use of these drugs were found to be similar to that seen with opioids, namely female gender, history of alcohol excess, depression and previous opioid use. Gabapentinoid use was also higher in the burn cohort pre-injury (6%) compared to the general population (4.1%), with their use increasing further after burn injury to 9.5%.

Lastly, for patients that survived to 30 days following burn injury, one in twenty died in the follow-up period to a maximum of four years. Multivariable Cox proportional hazards analysis demonstrated that increasing age and increasing comorbidity burden were associated with increased hazards ratios (1.06 and 3.51 respectively). As were the presence of airway burn or smoke inhalation (HR 2.8) and the pre-injury use of anxiolytic drugs (2.13).

The work presented in this thesis systematically reviews the existing evidence for neuropathic agents in managing burn-related pruritus; assesses a protocolised approach to managing such pruritus; outlines the epidemiology of burns in Scotland; describes the mortality from burns and the associated risk factors; describes the burden of pain and mental health conditions using drug prescription data as a surrogate measure of these conditions; and describes the factors associated with death in the years after surviving a burn injury.

This information may be used by clinicians to inform decisions regarding management of burn-related pruritus. This work also provides a deeper understanding of the complex interplay between mental health conditions, drug use, comorbidity burden and socioeconomic deprivation that often affect those that suffer a burn injury. It also highlights some of the important outcomes following survival of a burn injury with an increased risk of chronic opioid use, especially among those with certain characteristics.

Future research should focus on exploring the influence of the pathological effects of the burn injury compared to the high prevalence of pre-existing conditions that can similarly contribute to morbidity and mortality.