|Year : 2014 | Volume
| Issue : 1 | Page : 56-61
A study of prognostic factors for prediction of complications and outcomes in burn patients
Rahul Dalal, Col Alok Sharma, Brig B Chakravarty, Col M Alam Parwaz, Col Anil Malik
Department of Plastic and Reconstructive Surgery, Armed Forces Medical College, Pune, Maharashtra, India
|Date of Web Publication||15-Dec-2014|
Flat No. K-302, Queen's Tower, New D.P. Road, Aundh, Pune, Maharashtra - 411 007
Source of Support: None, Conflict of Interest: None
Aim: The aim of the present study is to evaluate various prognostic factors in burn patients and predict prognosis and mortality of patients on the basis of prognostic factors. Materials and Methods: A study was conducted on 10 adults, total body surface area burns of >40% (40-90%) sequential thermal burn admissions at Burns Center. Blood samples were drawn from day of admission to discharge. Results and Statistics: (1) Fatal outcome in four patients, persistent serum cholesterol <100 mg%. (2) The difference in cholesterol values in patients with fatal outcome and survivors was significant. On comparing median cholesterol values for non-survivors and survivors on post-burn day-7, there was statistically significant difference (P = 0.039) by Mann-Whitney U-test. Serum cholesterol was significantly lower in fatal cases. (3) Infection or sepsis in patients correlated with the presence of toxic granules, toxic vacuoles on peripheral smear, raised total leukocyte count and low values of serum cholesterol. (4) Echinocytes (spiculated red blood cells [RBC]) were seen in all patients. In four patients, they persisted from post-burn day 4 until death. Progressive decrease in echinocytes, which correlated with rising cholesterol values was seen in survivors. Conclusion: Poor outcome in burn patients is related to persistently low serum cholesterol, high serum triglyceride and presence of echinocytes, toxic granules, toxic vacuoles and high white blood cell counts or vice-versa.
Keywords: Cholesterol, echinocytes, total leukocyte count, toxic granules, toxic vacuoles, triglyceride
|How to cite this article:|
Dalal R, Sharma CA, Chakravarty BB, Alam Parwaz CM, Malik CA. A study of prognostic factors for prediction of complications and outcomes in burn patients. Indian J Burns 2014;22:56-61
|How to cite this URL:|
Dalal R, Sharma CA, Chakravarty BB, Alam Parwaz CM, Malik CA. A study of prognostic factors for prediction of complications and outcomes in burn patients. Indian J Burns [serial online] 2014 [cited 2019 Aug 24];22:56-61. Available from: http://www.ijburns.com/text.asp?2014/22/1/56/147007
| Aim|| |
The aim of the present study was to evaluate the behavior of serum cholesterol and triglyceride levels, echinocytes, toxic granules, toxic vacuoles and total leukocyte count (TLC) in the early and late phases of severe burns, in order to determine the statistical significance of these biochemical and hematological indicators for early prediction of post-burn complications or recovery.
| Introduction|| |
Thermal injury is caused by overheating of body tissues above the critical temperature, leading to tissue damage. An improved understanding of burn pathophysiology has contributed to improvement in fluid resuscitation, infection control, support of hypermetabolic response to trauma, nutritional support and early closure of the burn wound and burn outcome in general.  Thermal injury can cause many changes in the skin i.e., local response and in the body in general i.e., systemic response. The metabolic changes are important among systemic response.  The pathophysiology of the burn syndrome is characterized by the burn wound infection and the host's impaired defense to it, hypermetabolism and increased energy demand. Ominous post-burn complications are pulmonary insufficiency, renal insufficiency and complications involving the gastrointestinal tract.  Any biochemical or hematological markers which can predict poor outcome or complications will open a new vista to modify treatment strategies in order to improve outcome and decrease morbidity and mortality in major burn injury.
| Materials and methods|| |
Totally 10 consecutive thermal burn patients with 40-90% of total body surface area (TBSA) involvement were admitted to our burns center at a tertiary teaching hospital. Out of a total of 10 patients, five male and five female patients were studied with age range of 21-55 years and mean age of 31.8 years. Written/informed consent was taken from each patient or their relatives. The study was conducted as per ethical guidelines.
All patients received a uniform regime of treatment consisting of standard fluid resuscitation, nutritional support, plasma expanders, fresh frozen plasma and prophylactic antibiotic therapy. Wounds were dressed with topical silver sulfadiazine.
Blood samples were collected from all subjects by venepuncture on admission to burn center and after 24 h. Samples were collected daily for 1 st week and for patients developing complications and twice weekly thereafter until discharge from burn unit.
Diet consisted of high protein with balanced carbohydrate and fat diet to provide high calorie diet.
Energy requirement was calculated as per Curreri formula:
Age 16-59 years: (25) W + (40) TBSA
Age ≥60 years: (20) W + (65) TBSA
Enteral feeding was started within 24-48 h, and was given orally or through ryles tube.
Feeds were started with water, then diluted milk and then upgraded to burns high protein diet as tolerated by the patient, depending on condition of the patient [Table 1].
In the first 48 h no antibiotic was given for small area burns (<10% TBSA)
For large area burns with inhalation burns-on admission intravenous antibiotics were given
- Cefotaxim/amoxicillin-clavulanic acid
Later antibiotics were given as per culture and sensitivity.
Patients referred >24 h post-burn injury, burns <40% or >90%, electrical and chemical burn injury patients and patients with pre-existing co-morbid conditions.
- Serum cholesterol levels.
- Serum triglyceride levels.
- Presence of echinocytes, toxic granules and toxic vacuoles in peripheral smear.
- In-vitro diagnosis of total cholesterol in serum and plasma by - cholesterol oxidase-peroxidase method with Enzo Kit-liquid cholesterol reagents obtained from RFCL Limited, Dehradun, Uttarakhand, India.
- Low-density lipoprotein (LDL)-cholesterol assay by LDL-cholesterol reagent obtained from ERBA diagnostics Mannheim GmbH, Germany.
- High density lipoprotein (HDL)-cholesterol assay by HDL-cholesterol reagent obtained from ERBA diagnostics Mannheim GmbH, Germany.
- Trigycerides assay by - GPO-Trinder method end point, based on the method of Wako and modifications of McGowan et al. and Fossati et al., obtained from Transasia Bio Medicals Ltd., Baddi, Solan, H.P, India in Tech association with ERBA diagnostics Mannheim GmbH, Germany.
- Total leucocyte count study by Auto analyzer machine (SysMex KX-21, Kobe, Japan).
Expected cholesterol values, normal range 150-250 mg% (average 200 mg%) were based on the comprehensive age and sex-specific data from the general population.
White blood cell (WBC) response, presence of echinocytes, toxic granules, vacuoles, [Figure 1] and [Figure 2] cholesterol and triglyceride levels at the time of a culture-positive infection were recorded. The antimicrobial therapy was modified when there was clinical evidence of a new infection.
Data were analyzed with Statistical Package for the Social Science (SPSS Inc., Chicago, Illinois) for Windows (version 17) for quantitative data analysis. Data are expressed as means ± standard deviation to test changes in dependence on time after thermal injury, comparisons were performed using the Mann-Whitney U-test and P < 0.05 were considered to be significant. The unpaired t-test was used for correlation analysis. In all tests, P < 0.05 was considered as significant.
| Results and Statistics|| |
Fatal outcome was seen in four patients, with persistent serum cholesterol <100 mg%. The difference in cholesterol values in patients with fatal outcome and those who survived was significant. On comparing median cholesterol values for non-survivors and survivors on post-burn day-7, there was statistically significant difference (P = 0.039) noted (by Mann-Whitney U-test). Cholesterol was significantly lower in fatal cases [Figure 3] and [Table 2].
- TLC was significantly higher in non-survivors than in survivors at the time of admission but not subsequently. No significant difference in values was noted for triglycerides (TG), echinocytes, toxic granules and toxic vacuoles [Figure 4] and [Figure 5].
- Infection or sepsis in patients correlated with presence of toxic granules, toxic vacuoles on peripheral smear, raised TLC and low values of cholesterol.
- Echinocytes (spiculated RBC) were seen in all patients. In four patients they persisted from post-burn day 4 unil death. Progressive decrease in echinocytes which correlated with rising cholesterol values was seen in survivors.
- Mortality was seen in a case of TBSA 40% (lowest burn % death) while the highest burn percentage associated with survival was 63%. Fatal outcome in 04 cases: I = Post-burn day 7, II = Post-burn day 8, III = Post-burn day 10, IV = Post-burn day 24.
- Poor signs observed were:
- Decreasing serum cholesterol levels or failure to increase by 10% (a 10% Figure used for statistical analysis and data assessment).
- Increased serum triglyceride levels which fail to decrease progressively.
- Presence of echinocytes, toxic granules and toxic vacuoles on peripheral smear.
- TLC counts increased by 20% or >16000 and <4000.
| Discussion|| |
The degree of metabolic changes experienced by burn patients is directly related to the extent of injury. In large burn injuries, cortisol, glucagon and catecholamines are markedly elevated.  Cortisol is strongly catabolic and is associated with negative nitrogen and calcium balance, loss of tissue protein and bone mineral. It also stimulates gluconeogenesis, increases proteolysis and sensitizes adipocytes to the action of lipolytic hormones. Catecholamines increase the rate of glycogenolysis, hepatic gluconeogenesis, promote lipolysis and peripheral insulin resistance.  These changes lead to release of amino acids from muscles and lipolysis of adipose TG leading to the release of fatty acids into the plasma. The free fatty acids can be used directly by most peripheral tissues for their energy requirements.  In burn patients, fat oxidation is increased to obtain endogenous energy substrates. In addition to that, there is increased recycling of fatty acids that leads to increase in triglyceride plasma level.
Cholesterol is an inevitable component of almost all phospholipid membranes in the human organism. It occurs in both the free and ester form of cholesterol and fatty acids.
Free cholesterol is a component of cell membranes. Cholesterol in the organism originates both from the external environment by absorption from the digestive tract and by synthesis de novo from acetyl-CoA. Under normal circumstances, a significant portion of the required amount of cholesterol is obtained from food. Absorbed cholesterol from the diet is a component of chylomicrons and is directed as chylomicron remnants toward the liver. The hepatic cholesterol pools originating from chylomicron remnants (dietary cholesterol) and de novo synthesized cholesterol are combined and excreted as very low density lipoprotein (VLDL) lipoproteins. Intravascularly, VLDL converts to LDL lipoprotein and this particle is a major source of cholesterol for many tissues, specifically those undergoing frequent cell divisions. The maximal synthesis of cholesterol in a healthy human being varies in the range of 500-1000 mg a day. About 1 g of cholesterol is eliminated from the body per day. Approximately half of this is excreted in faeces after conversion to bile acids. The remainder is excreted as cholesterol. 
Dunham et al. in their study demonstrated that patients with severe trauma had a sudden reduction in total serum cholesterol concentration.  Hypocholesterolemia has been found in patients undergoing surgical interventions,  and in those with multiple organ dysfunction syndrome ,, and burns. , Fraunberger et al. demonstrated a relationship between hypocholesterolemia and several disease states, as well as organ dysfunction. In patients with multiple organ dysfunction syndromes plasma cholesterol below 100 mg/dl was associated with increased mortality (P < 0.05). A decrease in plasma cholesterol was also associated with increased circulating levels of tumor necrosis factor. 
Other authors have associated hypocholesterolemia with inflammatory states. ,
Nearly 30% or greater reduction in lipid and lipoprotein concentrations is known to occur in a variety of inflammatory states.  Interleukin-6 and tumor necrosis factor-α have been implicated as potent negative regulators of lipoprotein metabolism in-vitro, and in-vivo. ,
Coombes et al. documented an increase in triglyceride level and a fall of serum cholesterol level following severe burn injury.  Birke et al. demonstrated that the cholesterol level fell gradually after thermal injury and that these changes were proportional to the extent of burn trauma.  It is also seen that serum cholesterol correlates with organ failure and sepsis.  Proposed explanations for the development of hypocholesterolemia include down regulation of hepatic synthesis,  dilutional effects with resuscitation,  loss of apoproteins in burns after blister formation,  and metabolic utilization. ,
Hypocholesterolemia occurring with the development of infection was demonstrated during the 15-year period of the Kaiser Permanente study, conducted in 15,000 healthy men and women. 
In our study, we found similar reduction in cholesterol and increase in triglyceride levels, which can be attributed to increased energy demands, increased recycling of fatty acids, hyper metabolism due to release of cortisol, glucagon and catecholamines.
Ahmed SS  has done his study of comparison of three parameters i.e., difference in cholesterol, TG and HDL levels on burn patients in Iraq. In our study, the subjects studied are of Indian ethnic origin with different food habits compared with Middle Eastern population. Our study has five different parameters of serum cholesterol, TG, echinocytes, TLC, toxic granules and vacuoles. All these parameters were studied simultaneously in all patients. These parameters were selected on the basis of ease of availability of simple tests for detection and affordability. No previous study has been done on burned Indian patients regarding these parameters. Our study doesn't concentrate only on cholesterol but on all five parameters. The study was carried out with the basic idea that "Results of original research are not always consistent; studies of similar therapies may reach contradictory conclusions, especially in different populations." 
Infection or sepsis in burn patients in our study correlated with low cholesterol, raised triglyceride levels, presence of toxic granules and vacuoles and raised TLC.
Morphologic changes can be seen on the blood smear of a patient with severe thermal burn injury. Acute hemolysis, leukocytosis and thrombocytopenia are the most common abnormal hematologic findings. The severity of the hematologic abnormalities is most closely related to the extent and severity of the burn. Involvement of at least 15-20% of the body surface by third degree burns is typically associated with a severe acute hemolytic anemia. This hemolytic anemia is initially due to acute intravascular hemolysis followed by extravascular hemolysis and is associated with a wide range of abnormal red cell morphology. The most common abnormalities are the presence of spherocytes, schistocytes and echinocytes i.e., spiculated RBCs [Figure 6].
These abnormalities are due to the increased osmotic and mechanical fragility of erythrocytes following exposure to increased temperatures. The hemolysis is most severe within the first 24-48 h following exposure. Up to 30% of the red cell mass may be destroyed during this time period. Simultaneous with the insult to the red cells is increased vascular leakage due to changes in the endothelium. This results in decreased plasma volume secondary to an increase in fluid sequestration within the tissues and extracellular spaces. Patients are at high risk for intravascular shock and renal failure during this time. Initially a stress leukocytosis with a neutrophilia may be present due to the tissue damage associated with thermal burn injury.
Erythrocytes exposed to temperatures of greater than 47°C, undergo a variety of structural and functional changes. Changes to spectrin, one of the main proteins that make up the red cell cytoskeleton, results in intravascular globular fragmentation of the red cell membrane and the formation of membrane buds. These pieces and fragments produce schistocytes, with the largest fragment resealing its damaged cytoskeleton with resultant spherocyte formation. The shed buds become microspherules or tiny spheroidal red cell fragments. These changes result in increased osmotic and mechanical fragility and decreased cellular flexibility and elasticity. ,,,
In our study, echinocytes were seen in all burn patients. They gradually disappeared in survivor group but persisted in non-survivor group.
| Conclusion|| |
Poor outcome in burn patients was seen to be related to persistently low serum cholesterol, high serum triglyceride and presence of echinocytes, toxic granules, toxic vacuoles and high WBC counts in this study. A larger study may be of value perhaps to validate these findings and point the direction for modulation or intervention for improving survival in burns.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2]