|Year : 2018 | Volume
| Issue : 1 | Page : 48-54
The impact of first-day levels of serum proteins and lipids and their subsequent trends as prognostic indicators of burn mortality
Shobhit Gupta1, Sameek Bhattacharya1, Parul Goyal2
1 Department of Burns, Plastic and Maxillofacial Surgery, PGIMER and Dr. Ram Manohar Lohia Hospital, New Delhi, India
2 Department of Biochemistry, Plastic and Maxillofacial Surgery, PGIMER and Dr. Ram Manohar Lohia Hospital, New Delhi, India
|Date of Web Publication||11-Mar-2019|
Dr. Parul Goyal
Room No. 319, Administrative Block, PGIMER and Dr. Ram Manohar Lohia Hospital, Baba Kharak Singh Marg, New Delhi - 110 00
Source of Support: None, Conflict of Interest: None
Introduction: In severe burns, there is a profound systemic response that persists till the wounds heal. Since these physiological and metabolic derangements are dynamic over the clinical course of burns, it is expected that both trend of change and absolute values of the protein and lipid levels, to have a bearing on the prognosis and the ultimate outcome. Hence, this study was envisaged evaluate the prognostic value of these metabolic variables in burn patients.
Materials and Methods: The study conducted on 100 adult patients of thermal burn (20% and 60% total body surface area). Serum albumin, globulin, total proteins, cholesterol and triglycerides (TGs) were estimated on alternate days starting from day till discharge or death. The 1st-day value and the trend of serial values throughout the clinical course were compared among nonsurvivors and survivors.
Results: Mean serum values of albumin, globulin, and total protein on first-day of burns in survivor group were higher. Serum albumin levels of ≤2.1 g/dl at day one was a poor prognostic factor. The trend in the serum values of albumin, globulin, total protein, and cholesterol in survivor group was significantly positive and negative in nonsurvivors. Serum TGs, however, showed a nonsignificant negative trend in the survivors. Among the biochemical markers evaluated, most significant prognostic parameter was serum albumin, with maximum sensitivity and specificity.
Conclusion: The cutoff values of proteins and trend of subsequent serial values can guide metabolic manipulations, albumin infusion, and dietary intake. In addition, these biochemical parameters merit inclusion in burn prognostic index scales.
Keywords: Albumin, burns, lipids, prognosis, total protein, trends
|How to cite this article:|
Gupta S, Bhattacharya S, Goyal P. The impact of first-day levels of serum proteins and lipids and their subsequent trends as prognostic indicators of burn mortality. Indian J Burns 2018;26:48-54
|How to cite this URL:|
Gupta S, Bhattacharya S, Goyal P. The impact of first-day levels of serum proteins and lipids and their subsequent trends as prognostic indicators of burn mortality. Indian J Burns [serial online] 2018 [cited 2019 May 25];26:48-54. Available from: http://www.ijburns.com/text.asp?2018/26/1/48/253856
| Introduction|| |
Burn is defined as an injury to the skin and underlying tissues primarily caused by heat, electricity, friction, or contact with chemicals. However, its manifestations are systemic especially if burn surface area exceeds 15% total body surface area (TBSA). Burn mortality is more due to its metabolic and physiological derangements than due to the injury. Many burn mortality prediction models have been developed over time, which are important for quality control, assessment, planning of treatment, explaining prognosis, and as research tools to compare efficacy of different therapeutic modalities. Virtually, all burn mortality models include three variables: age, percentage TBSA burn, and inhalation injury in their analysis of burn outcomes. Although metabolic derangements are the cause of both morbidity and mortality in burns, most prognostic scoring systems do not include any of the biochemical parameters.,,, Severe burn injury is followed by a profound systemic response that persists till the wounds heal.,, These metabolic and physiological reactions include hepatic dysfunction, increase in vascular permeability, catabolism, and heightened inflammatory response.,,,, These ultimately affect serum protein and lipid levels in burn patients. The physiological and metabolic derangements in burns are dynamic over the clinical course. Hence, it is expected that the trend of change rather than the absolute values of the protein and lipid levels, to have a bearing on the prognosis and the ultimate outcome in these patients. There are various studies in the literature citing the relationship between serum proteins and lipids with the prognosis of burn patients; however, results are conflicting.,,,,,,,,,,,,,, Effect on the prognosis of baseline levels of biochemical parameters, serum trend dynamics, and the levels at which intervention is needed in burn patients is not covered in literature. Hence, this study was envisaged to tease out the effects of all these factors/variables on burn patients for determining and improving the prognosis. The study was conducted with the research hypothesis in mind as “low first-day serum protein and cholesterol levels and rising trend of triglyceride (TG) levels in burn patients, are associated with poor prognosis and can be used as prognostic indicator for burn mortality.”
| Materials and Methods|| |
The study was carried out in the Department of Burns, Plastic and Maxillofacial Surgery in collaboration with Department of Biochemistry from November 2015 to March 2017. This was a prospective, observational study conducted on 100 patients in the age group of 18–60 years suffering from thermal burn injury ranging between 20% and 60% TBSA. Relevant approvals had been obtained from the Institutional Review Board and the Ethics Committee (reference number: No. T.P [DM/MCh][18/2015]/IEC/9633). Burn patients admitted after 24 h of injury, electrical or chemical burns, or patients with inhalation injury or associated injury were excluded from the study. Preexisting hepatic and renal ailments and abnormalities of lipid metabolism were ruled by liver function test, kidney function test, and lipid profile respectively. All patients were treated conservatively as per the department protocol, i.e., daily dressing with 1% silver sulfadiazine cream till eschar separation or complete healing. Raw area after eschar separation was skin grafted when the patient was optimized for anesthesia and wound fit for grafting. Patients with hypoalbuminemia were treated with albumin infusions and plasma. All patients were put on enteral diet of at least 2500 KCal rich in carbohydrates and protein, and parenteral nutrition was reserved for patients in sepsis and ileus. The patients were grouped into nonsurvivors (Group A) and survivors (Group B). Serum albumin, globulin, total proteins, total cholesterol, and TGs were estimated on alternate days starting from day 1 of admission till discharge or death. The first sample was collected immediately on admission, and patient reporting after 24 h of burn were not recruited. For this 4–5 ml of whole blood sample was collected from each patient in serum separator gel tubes. Serum was separated by centrifuging at 3500 rpm for 10 min and serum proteins estimation was done on Fully Automated Dry Clinical Chemistry Analyzer, Vitros, 5, 1 by Ortho Clinical Diagnostics. The first-day value and the trend of serial values throughout the clinical course were compared in the two groups. Normal serum concentration, which will be taken as a reference value will be as follows:
- Serum total protein: 6.7–8.2 g/dl
- Serum albumin: 3.2–5.5 g/dl
- Serum globulin: 1.8–3.4 g/dl
- Serum TGs: 50–200 mg/dl
- Serum cholesterol: 130–220 mg/dl.
Sample size calculation
Serum albumin level as a risk factor for mortality inburn patients was studied by Olivia Alejandra Aguayo-Becerra, Carlos Torres-Garibay, Michel DassaejvMacýas-Amezcua, Clotilde Fuentes-Orozco, Mariana de Guadalupe Chavez-Tostado, Elizabeth Andalon-Duenas, Arturo EspinosaPartida, Andrea Del Socorro Alvarez-Villasen, Ana Olivia Corte s-Flores, Alejandro Gonzalez-Ojeda.
The study observed that the risk of mortality was significantly higher among patients with serum albumin <2 g/dL when compared with patients with serum albumin >2 g/dL (odds ratio [OR] = 25.8, P < 0.0001). Taking this value as reference, the minimum required sample size with 5% level of significance and 90% power of study is 22. To reduce the margin of error, sample size taken is 50. Moreover, we have done the study on 100 patients.
Formula used is:
Where Zα is the value of Z at two-sided alpha error of 5% and Zβ is value of Z at power of 90% and OR is odds ratio.
Following statistical tests were applied:
- Dependence of every predictor variable on time from admission to discharge/death will be evaluated by the Pearson's correlation coefficient for every patient
- A trend of variables over time of survivors and nonsurvivors will be tested by one sample t-test of the Pearson correlation with the reference value of 0, and difference between survivors and nonsurvivors will be tested by two samples t-test
- The risk of increasing or decreasing values of variables on survival will be assessed with the proportional hazard regression model of Cox
- Univariate and multivariate logistic regression analysis will be used to assess predictability of mortality by different risk factors by considering their day 1 value
- Receiver operating characteristic (ROC) curve will be used to find out the cutoff point of different risk factors in predicting mortality.
The value of each predictor variable in relation to time, in predicting mortality was evaluated by the Pearson correlation coefficient for every patient. Trend of variables over time in survivor and nonsurvivor groups was tested by one sample t-test of the Pearson correlation with the reference value of 0 and the difference between survivors and nonsurvivors was tested by two samples t-test. The risk of increasing or decreasing values of variables on survival was assessed with the proportional hazard regression model of Cox. Univariate and multivariate logistic regression analysis was used to assess the predictability of mortality by different risk factors by considering their day 1 value. ROC curve was used to find out cutoff point of different risk factors in predicting mortality. The results were considered significant with P < 0.05.
P < 0.05 will be considered statistically significant.
The data will be entered in MS Excel spreadsheet and analysis will be done using SPSS Statistics for windows, version 21.0, (IBM Corp., Armonk, NY).
| Results|| |
The study was conducted on 100 burn patients, and there were 83 survivors who were discharged in stable condition and 17 patients who expired during the course.
Average age of the patients in the survivor group was 41 years, and in the nonsurvivor group, it was 49 years. The average hospital stay in the nonsurvivor group was 21 days whereas it was 13 days in survivor group. Average TBSA in the nonsurvivor group was 50% ±5.59%, and in the survivor group, it was 34.76% ±8.76% [Table 1].
In the survivor group (n = 83), there were 46 female patients and 37 male patients, and in nonsurvivor group (n = 17), there were 11 female patients and 6 male patients. There were more number of female patients in both the groups; however, the sex ratio was similar in both the groups statistically with P = 0.48.
Mean serum values of albumin, globulin, total protein on first-day of burns in survivor group was 2.43, 2.53, and 4.96 g/dl, respectively. In the nonsurvivor group, the average serum albumin, globulin, and total protein were 1.85, 1.99, and 3.84 g/dl, respectively. This difference was statistically significant with lower levels of each parameter in nonsurvivor group. Similarly, on comparing serum lipids, it was seen that the day 1 levels of serum TGs and cholesterol were higher in survivors; however, the difference was not statistically significant [Table 2].
Cutoff value for day 1
The cutoff point of day 1 level of different risk factors in predicting mortality [Table 3].
|Table 3: Receiver operating characteristic curve for initial prognostication|
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Serum albumin levels of ≤2.1 g/dl at day 1 was considered as a poor prognostic factor with P < 0.0001 with sensitivity of 88.24 and specificity of 78.31, and area under the ROC curve (AUC) of 0.89. Serum globulin levels of ≤2.2 g/dl at day 1 was considered as a poor prognostic factor with P < 0.0001 with sensitivity of 76.47 and specificity of 77.11, and AUC of 0.84. Similarly, serum levels of total protein on day 1 ≤4.2 g/dl was considered as a poor prognostic factor with P < 0.0001 with sensitivity of 82.35 and specificity of 86.75, and AUC of 0.90. Day 1 values of serum TGs and cholesterol were not significant according to ROC curve, and the cutoffs cannot be used for prognostic purpose statistically.
Mortality as dependent variable for the variables taken on day 1 [Table 4].
With the increase in serum levels of albumin, globulin, and total proteins at day one by 1 g/dl each, risk of mortality significantly decreases by 99.4%, 98.3%, and 96.6%, respectively. Values of cholesterol and TGs at day one were not statistically significant.
The trend in the serum values of albumin, globulin, total protein, and cholesterol in survivor group was significantly positive with Pearson correlation coefficient of +0.64, +0.39, +0.65, and +0.67, respectively. In the nonsurvivor group, there was a significant declining trend in the serum levels with Pearson correlation coefficient of −0.63, −0.57, −0.8, and −0.6, respectively. However, the trend of serum TGs was exactly opposite to other variables which was +0.57 in nonsurvivors and −0.41 in survivors [Table 5] and [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5].
The mortality risk was assessed by increasing or decreasing values of albumin, globulin, total proteins, cholesterol, and TG [Table 6].
Increase in value of serum albumin with time significantly decreases the risk of mortality by 90.37%. Increase in value of serum globulin with time significantly decreases the risk of mortality by 95.20%. Increase in value of serum total protein with time significantly decreases the risk of mortality by 97.99%. Similarly, increase in value of cholesterol with time significantly decreases the risk of mortality by 87.97%. On the contrary, increase in value of TGs with time significantly increases the risk of mortality by 65.1%.
Predicting mortality according to the serum values during the course
The cutoff point of albumin levels during the course was found to be 1.6 g/dl at which area under the ROC curve was 1, signifying mortality chance of 100% with 100% sensitivity and specificity and P < 0.0001. Similar cutoff value of globulin levels during the course was 1.8 g/dl at which area under the ROC curve was 0.96 signifying very high chances of mortality with 88% sensitivity and 95% specificity and P < 0.0001. The cutoff point of total protein levels during the course was 3.9 g/dl with area under the ROC curve was 0.96 implying very chances of mortality with 100% sensitivity and 86.75% specificity and P < 0.0001.
The cutoff point of cholesterol was 78 g/dl with area under the ROC curve as 0.88 pointing at very high mortality below this at any point with 76% sensitivity and 91% specificity and P < 0.0001. However, the lowest and the highest values of TG were not significant statistically [Table 7].
|Table 7: Predicting mortality according to lowest values during the course|
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| Discussion|| |
Objective and real-time evaluation of prognosis in burns throughout the clinical course of patients is important to improve outcome. The earliest and simplest score predicting burn mortality included age and percentage TBSA. Subsequently, the Abbreviated Burn Severity Index was proposed, which is a five-variable scale including sex, age, inhalation injury, percentage of full-thickness burn, and percentage of TBSA. Chances of mortality in burns are also governed by many physiological and metabolic derangements which happen during the clinical course of the patients. It is a fact that the clinical course of burn injury is in constant flux owing to the physiological, metabolic, and inflammatory responses. Hence, metabolic parameters are expected to reflect the status of pathology and ultimately the prognosis of burn patients. However, none of the existing burn prognostic scales included any metabolic parameter.
In extensive burns, the hypermetabolic state continues for more than 2 years posttrauma. The response is characterized by increased metabolic rates, hypercatabolism, insulin resistance, multiorgan dysfunction, muscle protein degradation, and increased risk for infection. Hypoproteinemia during acute phase of burn is because of loss of protein-rich plasma to third space owing to increased capillary permeability and increase of free-radical oxidation of serum oxidatively modified proteins. Subsequently, the reduction in serum protein level in burn are because of various factors which include oxidation of albumin which causes an increase of platelet and erythrocyte aggregation and reduction of protein levels, loss from wound exudation, and acute phase response of plasma protein synthesis in the liver.,, In addition, there are hormonal imbalances affecting the liver which also have an impact on plasma cholesterol, TGs, and lipoproteins. Levels of catabolic glucagon and cortisol are elevated while there is suppression of insulin secretion due to raised catecholamines. This hormonal pattern leads to enhanced lipolysis, which in turn leads to low serum cholesterol and raised TG values, due to high levels of fatty acids., Hepatocellular damage has been regarded as one of the major causes of cholesterol reduction at later phase of burn. The hypercatabolic state in burns is dynamic, continues throughout the clinical course and is known to parallel the extent of burns, sepsis, and dietary intake. With these facts in mind, this study was undertaken with the hypothesis that, the baseline protein and lipid levels recorded at day 1 of burns and the subsequent trend of daily serum values throughout the course of treatment have tangible bearing on prognosis.
In the study, it was hypothesized that day 1 values reflected the basal nutritional level of the patient and the magnitude of third space sequestration of protein-rich plasma during acute phase. In the study, it was observed that patients who survived had a higher initial serum protein and lipid levels; however, the statistical significance of initial level serum protein was much higher than serum lipids. Hence, it can be deduced that the baseline serum proteins values recorded at day 1 of burns, reflecting the nutritional status, has prognostic value. However, in contrast, serum lipid levels at day 1, although higher in survivor group, did not have a statistically significant impact on prognosis of the patient. In our research, we could also deduce a cutoff value of 2.1, 2.2, and 4.2 g/dl of albumin, globulin, and total protein, respectively, below which the prognosis was very poor. The corollary was also proved, as there was reduction in mortality chance by 99.4% with 1 g/dl increase in albumin level at day 1. Comparing albumin and globulin, it was seen that day 1 value of albumin was a better predictor than globulin, but both could be used in prognostication. In a similar study, there was 24%–56% increase in burn mortality for each 2.5 g/dl decrement in serum albumin concentration. Aguayo-Becerra et al. studied the relation of albumin level at day 1 of burn with the mortality of burn patients and concluded that patients with levels <2 g/dl had high chance of mortality, which was comparable to the cutoff value of 2.1 g/dl, in our study. Ramos et al. also had a cutoff value of 2 g/dl below which mortality chance increased by 33%. On the contrary in a study by Miquet-Rodrıguez et al., there was no association of mortality with albumin level which could be because of small sample size. Jeschke et al. reported high protein turnover in burns although there was no correlation with mortality or prognosis of burn patients.
Most of the studies from literature cited above correlated only the day 1 levels of serum protein with mortality and not the trend of serial values during the subsequent clinical course. It was observed in our study that there was a significant positive trend of serial serum proteins and cholesterol levels in patients who survived and a gradual negative trend in patients who expired. This trend was reversed in TG levels, which was positive in nonsurvivors and negative in survivors. These trends can easily be explained by the hypercatabolic impact of burn injury in which there is hypoproteinemia and stimulated lipolysis due to increased glucagon and cortisol levels, suppression of insulin secretion, and peripheral insulin resistance. It could be statistically inferred that the increase in values of albumin, globulin, total protein, and cholesterol during the clinical course reduces the mortality by 90.37%, 95.20%, 97.99%, and 87.97%, respectively, with total protein acting as the best predictor and cholesterol the worst. In contrast, it was seen that increase in value of TG with time significantly increases the risk of mortality by 65.1%.
In the study, we could also infer that if the albumin level fell below 1.6 g/dl any time during the clinical course, mortality was almost certain with 100% sensitivity and specificity. Similar values for globulin and total protein were 1.8 g/dl and 3.9 g/dl, respectively. The sensitivity of total protein cutoff value was as good as serum albumin, but specificity of both globulin and total protein cutoff values were lower than albumin. The cutoff value of cholesterol when taken as 78 mg/dl, specificity of having a poor prognosis was very high but sensitivity was low. TGs values during the course were not statistically significant.
There were very few studies in the literature citing the relationship of serum lipids with the prognosis of burn patients. Although studies have been done on critically ill, sepsis, and hospitalized patients, all these studies basically concluded that mortality was associated with low cholesterol levels. However, contrary reports are also there documenting hypercholesterolemia in hospitalized patients with sepsis, malignancy, acute kidney injury, and diabetic patients. Pertaining to burns, few studies report rise of serum cholesterol in first 7–10 days but none of these studies correlated cholesterol levels with mortality and prognosis, and none dwell on serum TGs levels. Coombes et al. also reported fall in serum cholesterol and rise in serum TGs in severe burns without commenting on its bearing on prognosis. Only a study by Kamolz et al. is close to correlating cholesterol and TG level with mortality. They reported lower cholesterol level among nonsurvivors compared to survivors and high TGs levels among nonsurvivors, but normal TG levels among survivors.
| Conclusion|| |
In the study, among the biochemical markers evaluated, most important prognostic parameter was found to be serum albumin, whose day 1 value and subsequent trend during the course were significantly different among survivors and nonsurvivors groups, with maximum sensitivity and specificity. The findings of the study, especially those pertaining to protein levels, are in-spite of regular plasma, albumin, and amino acid infusion as per the standard of care. Hence, the cutoff values of proteins open an objective indication for intervention in the form of more aggressive parenteral protein and albumin infusion. The cutoff values of proteins at day 1 can be an early warning to initiate plasma and albumin infusion. Similarly, trend of subsequent serial values can guide metabolic manipulations, albumin/amino acid infusion, and dietary intake of patients. In addition, apart from physical parameters, biochemical parameters such as serum albumin levels merit inclusion in burn prognostic index scales.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]