Prognostic indicators in acute burned patients-a review

Sherif EmaraPlastic Surgery Department, Helwan Univesity Hospital, Badr City, Cairo, Egypt

Prognostic indicators in acute burned patients-a review

Sherif Emara*
Plastic Surgery Department, Helwan Univesity Hospital, Badr City, Cairo, Egypt

ARTICLE INFO ABSTRACT

Article history:

Received in 6 February 2015

Received in revised form 7 February 2015 Accepted 8 February 2015

Available online 10 February 2015

Keywords:

Burn

Prognostic indicator Outcome

Morbidity

Mortality

Burn trauma is in need for prognostic indicators or admission scores. This aims for realistic documentation of the burn injury, expectation of the prognosis, and to facilitate a patient stratification to evaluate therapeutic strategies. A computer search through different medical websites was performed looking for articles correlating prognosis with different burn indices. These were carefully summarized and analyzed for this review. Variable studies were found related to that issue; the reliable indicators found had been classified as general or specific. All of them had certain clinical importance, but limitations are a common feature. All the listed indices are useful to serve in the only special clinical situations. We couldn’t claim that they are actual prognostic indicator in burn victims. We believe that we still lack the proper prognostic indicator in burn patients. Researchers are invited for more effort to organize a more reliable prognostic indicator and scoring system for burn patients.

Tel: +201145999930

E-mail: dremara@emara.com

1. Introduction

Scoring systems for immediate post-traumatic patient evaluation, classification and outcome prediction have gained increasing acceptance during the past three decades. Among the wide variety of scores, the injury severity score, trauma score and the Glasgow coma scale have found widespread recognition[1]. The importance of burn prognostic indices lies not only in the prediction of outcome of an individual patient, but also in the distribution of the patients in comparable groups of severity for therapeutic and research purposes. Although the realistic prediction of the outcome of an individual patient is the first and main question of a patient’s family, the quantitative measurement of a patient’s illness using these indices is of great importance for the burn centre in deciding its therapeutic policy, evaluating new therapy and the quality of patient care, and estimating the cost of their services. The more accurate an index, the more useful it is for this latter purpose. For this reason, nowadays, several burn indices based on different statistical methods have been analyzed in an effort to make them more accurate in their predictions. Nevertheless, the accurate prognostic index in a burn centre is achieved either by using one of the known indices adopted to its particular needs and conditions or by producing its own new index and updating it continuously[2].

2. Methods

This is a review work aiming to gather the different burn indices in one article. A computer search using the internet websites was performed. A structured literature search in Medline, Embase, Pub Med, Clinical Evidence,and the database of library of Ain Shams University hospitals had been performed. The used keywords were “burn patient”, “assessment”, “prognostic”, “risk factor”, “index”, “indices”, “morbidity”, “mortality”, “outcome”and “death”. In addition to that, reference lists of related journal articles, key journals and existing reviews were also searched for additional data. All used articles were in English or with English translation of the abstracts.

After data collection, we classified the most reliable resulted parameters into two groups: general and specific prognostic indices. The general prognostic indicators are concerned mainly with the patient’s general status, burn wound condition and the potential of overall mortality. In the other group, researchers were found to investigate only a single parameter in burned patient. Others examined a single parameter in certain patient’s groups as in pediatric burn, inhalation injury, electric burn, etc.

3. Classification of prognostic indicators

Analysis of the search results identified various articles dealing with the burn prognostic indicators. With respect of the researcher’s opinions regarding the importance of their investigated parameters, classification and documentation of these articles formed the bulk of this review.

3.1. General prognostic indicators

The first burn score was developed in 1902 by Wiedenfeld who correlated total burned surface area (TBSA) and age with the mortality of his patient population (TBSA+Age ≥ 100; this carries poor prognosis). The same parameters were employed in the pioneering work of Bull and Squire in 1949[3].

Tobiasen and colleagues presented the abbreviated burn severity index in 1982, based on a multivariate logistic regression model[4]. This score included for the first time additional parameters, such as gender, presence of third degree burns or inhalation injury.

The size and depth of burn and patient age are useful for early prognostic indicators in burned patients, but have limited value in predicting mortalities. The objective of another study was to identify additional variables in the first 10 days of burn injury which could better predict patient outcome[5]. The regression analyses revealed that patient age and burn size were significant predictors of mortality on admission and throughout the first 10 days postburn. In addition, absolute monocyte count, absolute lymphocyte count, maximum daily temperature, and blood urea nitrogen were also significant predictors. These data indicate that logistic regression models can identify simple prognostic variables in burned patients which may improve clinicians’ ability to identify high-risk patients early in the course of their burn injuries[5].

Mortality predictive factors of burned patients are analyzed in 1 929 patients. Among the variables studied (TBSA, deep burn area, superficial burn area, age, sex, burn location, preexisting disorders), two only, deep burn area and age, have been retained as predictive factors which, when associated, allow to classify 94.47% of the patients in either survival or death group[6].

A study aimed to define the clinical, microbiological and laboratorial predictors of mortality with a view to focus on better burn care. Mortality rate was 5.0%; it was higher in elderly, larger burn area, presence of fungi and the presence of multi-resistant bacteria in the wound[7].

Stavropoulou and colleagues had a study on a 342 burned patients[2]. They compared the reliability of the usual burn indices with the APACHE II severity score in prediction of mortality. The study resulted in forming a new prognostic index, which is more accurate in the prediction of mortality, because it considers objectively and in detail the patient’s general condition on admission. APACHE III score had been suggested by Tanaka and colleagues to be used as a more efficient predictor of mortality in burn patients[8].

Another study evaluating the prognostic factors in severely burned patients was done by Danilla and colleagues evaluating multiple variables[9]. Pre hospitalization variables (burn injury of the respiratory tract, early intubation, fasciotomy, prompt fluid restitution), initial surgical attention variables (early escharectomy, fasciotomy, compartmental syndrome release, allogeneic skin grafts), and intra-hospital complication variables (acute renal failure, mechanical ventilation, shock, sepsis, etc.). The results of this study stated that prompt fluid restitution was the most important prognostic factor of pre hospitalization variables; burn injury of the respiratory tract was not statistically significant. Early escharectomy is a strong protective factor of the initial surgical attention variables. Compartmental syndrome, fasciotomy, and the use of allogeneic skin grafts are not associated with changes in survival. Mechanical ventilation, acute renal failure, shock and multiple organic failure are nosocomial complications associated with higher mortality[9].

A new study was done to investigate the possibility of using supervised statistical models (the orthogonal projections to latent structures) to assess burn injury patterns, outcomes and their interrelationship. Femalegender, higher TBSA, lower limb burn and intentional burn injuries fell in the high-risk class[10].

3.2. Specific prognostic indicators

3.2.1. Creatine kinase (CK) in electrical injury

Serial serum CK and creatine kinase myocardial band (CK-MB) isoenzyme levels were obtained from 116 of 125 electrical burn patients. Highly elevated CK and CK-MB were found to be associated with longer hospitalization and a greater risk of skin grafting or amputation, than with levels less than 400 IU/L[11].

3.2.2. Serum calcitonin in inhalation injury

One of the principal causes of death from burns is inhalation injury. The pulmonary neuroendocrine cell contains and secretes immunoreactive calcitonin (iCT), and, under the influence of various irritative stimuli, can be induced to secrete iCT in excess. A prospective study of serum iCT levels in 41 patients with burns was undertaken. Mean serum iCT levels were four times normal values at the time of admission and reached 31 times normal values by 24 h after injury. These levels did not correlate specifically with burn size. However, serum iCT had a very strong positive correlation with mortality, and in addition, was highest in patients who died early due to pulmonary injury compared with those who died later. In addition, serum iCT correlated positively with the need for mechanical ventilation and may be an important marker for the presence of inhalation injury, as well as a prognostic indicator[12].

3.2.3. Tumour necrosis factor-alpha (TNF-α)

TNF-α levels were studied in 42 patients with burns more than 20% TBSA. It was found to be poorly correlated to the burn wound depth and extent especially in the early post burn period. In contrast, the maximum plasma TNF-α level over the whole clinical course was significantly correlated with the extent of the burn and the prognosis[13].

3.2.4. Procalcitonin (ProCT)

Forty burn patients with TBSA ＞30% were studied, of whom 33 suffered an inhalation injury. That is to evaluate the significance of circulating ProCT, IL-6, TNF-α and endotoxin levels early after thermal injury. All patients had increased ProCT and IL-6 levels without any proven infection. ProCT and IL-6 levels correlated well with the severity of burn injury. ProCT levels are not correlated with smoke inhalation. ProCT and IL-6 were found to be a reliable prognostic indicators of mortality at the time of admission but less reliable than the clinical status[14].

3.2.5. Platelet count

Total platelet count was observed in 32 cases of major burn patients. A consistent correlation was noticed between the total platelet count, the presence of burn wound sepsis and the final outcome. The platelet count decreased initially in all cases of burn wound sepsis. It later on rose to normal in those who survived, while maintaining the downward trend in non-survivors. Thus the declining platelet count in burn patient is a useful prognostic indicator[15].

3.2.6. Serum lactate

Clinical studies document correlation of serum lactate and base deficit with mortality in trauma and sepsis. Resuscitation data from 49 patients admitted to an adult Burn ICU were analyzed. Lactate and base deficit were investigated upon admission and every 2 hours during the initial 48 h after admission. The authors found that two variables were predictive of mortality by the Cox regression model, serum lactate and patient age. Furthermore, analysis by logistic regression revealed that the initial serum lactate value was separately predictive of mortality[16].

3.2.7. Procalcitonin

To determine whether changes in ProCT could be used to predict the onset of sepsis, daily ProCT levels were monitored in 20 burned children. Analysis indicated a ProCT rise of 5 ng/mL or greater as the best indication of sepsis. The ProCT assay had a sensitivity of 42%, a specificity of 67%, and an efficiency of 57%. They conclude that ProCT is not as effective as CRP and/or platelet count in the early detection of sepsis in burned children[17]. Whereas a recent study done by Lavrentieva and colleagues showed that the maximum ProCT level had a prognostic value in burn patients and was considered to be an independent predictor of ICU mortality in a logistic regression analysis[18].

3.2.8. Interleukin-8 (IL-8) and interleukin-10 (IL-10)

In a study investigating the course of a pro-inflammatory cytokine IL-8 and an anti-inflammatory cytokine IL-10 in burned patients, there was an increase in serum IL-8 levels, and a peak level was detected shortly after burn injury. The peak IL-8 value of the non-survivors was greater when compared with that of the others. On admission, a significant difference in serum IL-8 values was found between survivors and those who died. In allpatients, a peak level of IL-10 was detected between 5 and 9 days of injury. In non-septic survivors, this peak level was less when compared with that of the others. After this peak level, in all patients, serum IL-10 levels showed a decrease, but in non-survivors, a second peak level was detected. They concluded that IL-8 and IL-10 were prognostic factors in burn sepsis[19]. The same conclusion was almost addressed recently by Csontos and colleagues[20].

3.2.9. Erythroblasts

A study included 464 consecutive burn patients, of whom 81 did not survive their injuries (17.5%). The mortality rate of patients with erythroblasts in peripheral blood amounted to 56.6% which is significantly higher than the mortality rate of patients without erythroblasts. None of the patients with more than 1 000 erythroblasts X 106/litre survived. The detection of erythroblasts in the peripheral blood of burn patients is highly predictive of death. Erythroblasts were detected for the first time around sixth day after admission and seven days before death[21].

3.2.10. Plasma cell-free DNA

Blood samples were collected from 28 burn patients within 24 h of injury and from 12 control subjects. Plasma cell-free DNA was measured by real-time quantitative polymerase chain reaction (PCR) assay for the b-globin gene. Samples were taken at a mean time of 5.7 hours after injury from 13 patients with flame/flash burns and 15 patients with scalds. Plasma DNA levels correlated with the length of hospital stay, but not with admission to the ICU nor the length of ICU stay. DNA levels correlated with the burn surface area and the number of operations needed for scalds, but not for flame/flash burns. DNA levels were higher in flame/flash patients than in scald patients; the difference may provide an objective indication of burn depth and inhalation injury[22].

3.2.11. Bacteremia or pneumonia

The etiology of bacteraemia or pneumonia as a prognostic factor for death in burn patients was studied, after a 10-day admission in ICU. The overall mortality was 15.8%. It was found that it is statistically significant risk factor if the patient was infected by either Acinetobacter or S. aureus, but that risk was maximum if a burn patient was infected by both types of microorganisms[23].

3.2.12. Early coagulation disorders

A study was done to evaluate the time course of coagulation markers in the early postburn period and clarify the role of coagulation alterations in organ failure and in mortality prognosis. Significant differences in the time course of coagulation markers were observed between survivors and nonsurvivors. Presence of overt DIC was related to mortality. Anti-thrombin, protein S, plasminogen activator inhibitor 1, and the Sequential Organ Failure Assessment score on Day 3, protein C on Day 5, and thrombin/antithrombin complexes on Day 7 revealed a real prognostic value for ICU mortality. Severe thermal injury is associated with the early activation of coagulation cascade, presence of DIC, organ failure, and increased mortality[24].

3.2.13. Triiodothyronine

Retrospective evaluation of free triiodothyronine (fT3), free thyroxine (fT4) and thyroid stimulating hormone (TSH) in 295 consecutive burn patients admitted to the Burn Unit was done comparing hormone levels in survivors and non-survivors. It was found that low fT3 levels were associated with poor outcome in burn patients. Hence, fT3 measurement could be proposed as a strong and costeffective tool of poor prognosis[25].

3.2.14. Serum creatine phosphokinase in electrical burn

The mean difference of serum creatine phosphokinase according to the extent of tissue damage and prognosis of the patients suffering from electrical burn injuries was studied on 38 patients. A statistically significant association was found between the level of serum creatine phosphokinase and likelihood of death[26].

3.2.15. Acute-phase plasma base deficit

Plasma base deficit was investigated to predict burn patient outcome. Patients admitted within 6 h of injury were classified into two groups. Mortality rate in Group A (plasma base deficit was less than or equal to -6; more negative) was significantly higher than Group B (plasma base deficit greater than -6). The authors concluded that it can be used as a valuable marker in the resuscitation of burn patients, along with clinical criteria[27].

3.2.16. T-lymphocytes

T-lymphocytes of 50 major burn patients were analysed in base line samples at 24 h and at 1 week and 2 weeks after burn. Recorded values were compared with 50 healthy controls. The obtained data were suggestive of persistent activation of T-lymphocytes two weeks after major burns whereas early shedding of β2-macroglubuline is related to activation of lymphocytes increasing their susceptibility toapoptosis, both indicative of altered immune response and consequent poor prognosis[28].

3.2.17. Microalbuminuria

Microalbuminuria as simple test was declared to be an indicator of widespread endothelial dysfunction and a predictor of morbidity in certain medical scenarios[29,30]. It was recently studied in our burn unit with multiple variables which are usually encountered during burn management. Microalbuminuria was found positive in patients with inhalation injuries (100%), systemic inflammatory response syndrome (88.4%), burn sepsis (95.1%) and postoperatively (94.9%). Microalbuminuria is the only simple, non-invasive, bed-sided, immediate and cost-effective test to indicate for occurrence of systemic inflammatory response syndrome if the other variables were stabilized[30].

4. Conclusion

This systematic review was carried out aiming to find a reliable prognostic indicator in burned patients. Many indicators and scores are valuable for trauma patients, yet this is not the case in burns. The currently available estimates of trauma injury rates fail to include burnstrauma[31]. This may poorly explain the lag of burn injury indicators behind the well-established general trauma indicators. Our need to find a proper prognostic indicator or a reliable scoring system for burn patient is a great hope that all burn care providers have been dreamt of.

The first simple prognostic score developed by Wiedenfeld in 1902, is still working and believed in many burn centres of developing countries[3]. Many studies have been found through our search, some of them had been concerned with the same parameters, and others even did not report the same outcome. Overall, many trials did not adequately state clear patient clinical variations which may affect their result, or provide sufficient information to facilitate its classification according to importance in predicting patient outcome. That is why we thought about classification of parameters into general and specific indicators.

Most of the included clinical researches were either did not mention or highly varied in burn wound criteria, and management protocol, and also mostly were of small sample size, with only four studies having more than 100 participants[18,21,23,25]. Small trials may overestimate effect size and may be unable to detect small differences[32].

Studies concerned with specific indicator were mostly investigating for inflammatory response mediators, except studies for Creatine kinase[11], creatine phosphokinase and plasma cell-free DNA, although all shared the same concept of directly or indirectly locking for extent of tissue damage[22,26].

Follow up of any of the mentioned indicators will demonstrate that it is useful in an only certain clinical situations, and cannot be solely considered as a reliable prognostic indicator for burn patients. As well, most of them require sophisticated, costly and time consuming analytic process, except two studies: platelet count and microalbuminuria[5,30].

We had attempted to reduce retrieval bias by conducting a methodical literature search for the published studies with no language restrictions. Nevertheless, we did not search the literatures published in languages other than English without supplementary English summary. Thus, it is inevitable that some publications might be missed.

Our review found that the data obtained was not reliable enough to make a firm conclusion on the efficiency of whichever mentioned parameters as a prognostic indicator in burn outcome. It is suggested that future randomized controlled studies using common and clinically relevant end-points to evaluate and look for a new, reliable, effective and readily available prognostic factor or scoring system to our burn victims are mandatory.

Conflict of interest statement

The authors report no conflict of interest.

Acknowledgement

I’m very grateful to Professor Osman Fathy, for his meticulous revisions and valuable advices to finalize this work.

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*Corresponding author:Dr. Sherif Emara, Plastic Surgery Department, Helwan Univesity Hospital, Badr city, Cairo, Egypt.

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