Characteristics And Outcome Influence Of Increased Plasma Triglyceride Level In Severely Burned Adult Patients

Summary

The aims of this study were to investigate the profile of serum triglyceride level and its influence on outcomes in adult patients with severe burns. An observational study was conducted on 62 patients with burn extent from and over 20% TBSA. Results indicated that serum triglyceride level steadily increased from 1.9mmo/l on the 3rd day to 2.5 mmol/l on the 14th day before reducing on the 21st day after burn. Remarkably higher triglyceride level was seen in patients with full thickness burn area >20% TBSA and in inhalation injury (p < .05). Liver size significantly increased over time and was greater in increased triglyceride patients, but the difference was not significant (p > .05). In addition, patients with elevated serum triglyceride level had significantly higher rates of multiple organ failure and death compared with the remaining group. Further studies need to be conducted to understand and determine intervention for increased plasma triglyceride levels in severely burned patients.

Introduction

In severe burn injury, hypermetabolic response starts 72 hours after burn. The degree of hypermetabolic state is considered to be the largest compared to any other type of injury or surgery.^1,2 The mobilization and utilization of fat from stores are increased as the result of increased secretion of hormones such as catecholamine, glucagon and cortisol, which lead to the release of free fatty acids from fat tissue.^3,4 Recently, increased serum triglyceride (TG) level of hospitalized patients has generated concerns.^5,6 Elevated serum TG level may be associated with impaired organ function and negative outcomes, but the real implication is still controversial. ^7,8,9 The purpose of this study was to assess the changes and impacts of increased serum TG level on outcomes of severely burned adult patients.

Patients and methods

An observational study was conducted on 62 severely burned adult patients admitted to the burn intensive care unit of the National Burn Hospital, Hanoi, Vietnam from August 2016 to August 2018. Selected criteria included age from 16 to 60 years old, burn surface area from and over 20% total body surface area (TBSA), admission within 72h after burn. Exclusion criteria included patients under 16 or over 60 years old, patients with concomitant trauma, comorbidity, pregnancy, admission more than 72 hours after burn or death within 72 hours post burn. Plasma level of TG was determined on the 3rd, 7^th, 14^th and 21^st day after burn. Plasma TG level ≥2 mmol/l was considered as increased TG. Liver size was determined by ultrasound on admission day and on the 21^st day after burn in 34 patients who did not suffer full-thickness burn on the upper abdominal area. All patients received the same management regime. Standard treatment included early excision and grafting with auto and allo-skin grafts. Enteral feeding was applied within 24 hours of admission. Data were collected, tabulated and analyzed to determine change in serum TG level over time. Relationship between plasma TG concentration and age, gender, burn features, liver size, rates of multiple organ failure (MOF) and death were also analyzed. Stata software version 14.0 was used with p value <.05 regarded as the significant level. This study was approved by the hospital’s Human Research Ethics Committee.

Results

Among the 62 patients, men were predominant (46 patients), with an average age of 35.2 ± 10.9 years, burn extent of 50.9 ± 17.4% TBSA and deep burn area of 19.3% ± 16.4% TBSA. Inhalation injury was diagnosed in 8 (12.9%) patients with overall mortality rate of 17.7% (Table I).

Table I. Patient demographic (n = 62).

The plasma TG level on the 3rd day was in the normal physiological range, increased to peak level on the 14^th day (p < .05 as compared to that on the 3rd day), then decreased on the 21^st day after burn, but was still higher than the normal value (2 ± .1 mmol/l). The highest proportion of patients with increased plasma TG level was 52.5%, which was recorded on the 14^th day after burn (Table II).

Table II. Serum TG level along the time after burns.

Plasma TG levels were not remarkably affected by age, gender or burn extent (p > .05) but were significantly higher in patients with full thickness burn area >20% TBSA on the 7^th and 14^th day after burn and in patients with inhalation injury on the 21^st day after burn (Table III).

Table III. Distribution of plasma TG level (mmol/l) to patients and burn features.

Liver size of 34 patients was in the normal physiological range on admission, then significantly increased on the 21^st day and was greater in increased TG patients, but the difference did not reach significant level (Table IV).

Table IV. Relationship between TG level and liver size (n = 34).

The relationship between TG level and outcome is shown in Table V. As can be seen, the serum TG concentration on day 3 after burn was not significantly different between patients with or without MOF or death (p > .05). From day 7 of burns onwards, serum TG levels were significantly higher in patients who developed MOF and died than in those without MOF or survivors (p < .05). Moderate correlations were recorded between TG level and MOF as well as mortality rate.

Table V. Relationship between TG level (mmol/l) and outcomes.

Discussion

Lipids in the body are mostly in the form of triglycerides (compound of glycerol and fatty acids), and are the main source of energy. Lipid and plasma lipoprotein metabolism is a complex process. Lipoproteins are divided into four groups including chylomicron, very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL). The majority of chylomicron and VLDL forms are triglycerides, while HDL and LDL are composed mainly of cholesterol and phospholipids. The liver and intestines are the main places to synthesize plasma lipoproteins. Accordingly, lipids are absorbed from the digestive tract, combined into chylomicron and then transferred into the bloodstream. Once circulating, the chylomicron is mainly delivered to the adipose tissue and the small part to the liver. The stored fat is only temporary, and always renewed and mobilized into the bloodstream mainly in the form of free fatty acids, triglycerides and phospholipids. The elevated serum TG concentration is mainly due to increased free fatty acids that are released by lipolysis simulating in adipose tissue due to adrenergic hormones, inflammatory cytokines, and to reduced plasma TG clearance rate.^5,10

Recently, increased plasma TG and its influence on outcomes has generated more concern.^11,12 Elevated serum TG level has been reported among critical patients with worse outcomes, especially in septic or septic shock patients. However, controversy still persists across the studies.^13,14,15 In 2019, Rashwan et al. reported that, compared with healthy people, serum TG level was remarkably higher in the septic patients on the first and third day of septic onset and prolonged to the 14^th day.¹⁶ Study by Lee et al. indicated elevated serum TG levels associated with mortality in septic patients.¹⁷ However, recent study by Fahila et al. indicated that there was no specific connection between the severity of sepsis and plasma triglyceride concentration in a patient with sepsis, and there was no significant difference in TG value on days 1- 5 between sepsis and non-sepsis patients.⁸

Dyslipidemia after burn injury is one of the key changes.^1,2,3 In severe burns, over 70% of the free fatty acid is released as an oxidized form, which is then re-esterified in the form of TG. Increased serum TG levels associated with massive release of metabolic hormones and cytokines can damage organs and influence burns outcomes. To the best of our knowledge, the first report on plasma TG levels in burn patients was by Birke and colleagues in 1965. They found no statistically significant changes in TG in burn patients.^18,19 Then, elevated plasma TG was first confirmed by Coomber et al., who determined increased plasma TG occurring 4 – 6 days after burn, parallel with a dramatic decrease in cholesterol and phospholipid levels in moderate burn patients.^20,21 In 2017, Khubchandani and colleagues compared the plasma TG levels of healthy people and burn patients and found that serum TG concentration was significantly higher in burn patients in the 3^rd week after burn (186 ± 20.19mg/dl vs. 164 ± 9.11 mg/dl; p < .05). In addition, serum TG level increased to 16% on the third week compared to the first week after burn.²² Study by Kraft and colleagues on 219 paediatric burn patients with second and third degree burns between 30 and 70% TBSA indicated that 63 patients, accounting for 28.8%, experienced an increased plasma TG with an average level of 231mg/dl.²³ Our results were in accordance with the above studies, with a high rate of patients suffering increased triglyceride levels (≥ 2mmol/l) during the first 3 weeks after burn.

Severe burns cause disorders of the organs, including the liver.^1,4 Numerous studies suggested that an increase in liver size after severe burn was due to an increase in the amount of TG in the liver and due to post-burn liver edema.²⁴ Barow et al. reported that patients who die 7 days after burn had an increase in liver size of up to 406%, mostly due to fat accumulation. ²⁵ Jeschke and colleagues reported an increased liver size that reached peak level at the second week postburn (220%) and remained at high levels until discharge.²⁶ Barret et al. studied fatal burn patients and found that 81% of them suffered fatty liver.²⁷ In 2005, works by Barrow and colleagues on children revealed that TG contributed up to 70% of the total fat in severity of hepatomegaly, and 85% to 90% of the hepatomegaly observed in severely burned children was associated with hepatocyte enlargement, which includes up to 19% intracellular fat.²⁸ In recent study, significantly increased liver size was seen in the 3rd week after burns and liver size was higher in increased TG patients, but we cannot find the significant difference between patients with and without increased serum TG level. The reason could be that not all studied patients were examined by ultrasound due to the presence of full thickness burn injuries on the upper abdomen and the number of patients was quite small.

Influence of elevated serum TG on outcomes after burn has also been reported. Kraft et al. studied 219 patients with severe burns and found that serum TG concentration increased in relation to organ damage and worse outcomes.²³ According to Dalal et al., clinical adverse outcomes of burn patients were associated with increased TG levels.²⁹ Kamolz et al. found an increase of TG in all non-survivors but not in the group of survivors, and concluded that ongoing measurements of serum lipid parameters could provide useful information for the clinician treating patients with severe burns.³⁰ In our study, patients with elevated serum triglyceride level had a significantly higher rate of multiple organ failure and death compared to the remaining group, and moderate correlations between serum TG concentration with MOF and death were also determined.

It is noted that propofol, which when used in anaesthesia may influence serum TG level, was often not mentioned in many reports.^31,32,33,34 Burn patients experience daily dressing change and numerous operations for debridement, necrosis excision and skin grafting. In our study, serum TG levels could not be affected by this issue as all blood samples were taken at 6-8a.m. before any procedures requiring anaesthesia. In addition, we only use intravenous ketamine or pain killer medications such us tramadol, or morphine for dressing changes.

Conclusion

We have shown that in severely burned adult patients, increased serum TG level is common. Elevated serum TG level can lead to significantly higher risk of multiple organ failure and death. It is necessary to conduct further studies to understand and determine intervention for increased plasma TG in severely burned patients.