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IF in 2008: 0.858
Chinese Medical Journal, 2007, Vol. 120 No. 20 : 1783-1787
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Characteristics of and strategies for patients with severe
CHAI Jia-ke, SHENG Zhi-yong, LU Jiang-yang, WEN Zhong-guang, YANG Hong-ming, JIA Xiao-ming, LI Li-gen, CAO Wei-hong, HAO Dai-feng, SHEN Chuan-an, TUO Xiao-ye, LIANG Li-ming, WANG Shu-jun
CHAI Jia-ke Burns Institute, First Hospital Affiliated to the General Hospital of People’s Liberation Army, Beijing 100037, China; SHENG Zhi-yong Burns Institute, First Hospital Affiliated to the General Hospital of People’s Liberation Army, Beijing 100037, China; LU Jiang-yang Department of Pathology, First Hospital Affiliated to the General Hospital of People’s Liberation Army, Beijing 100037, China; WEN Zhong-guang Department of Respiratory Medicine, First Hospital Affiliated to the General Hospital of People’s Liberation Army, Beijing 100037, China; YANG Hong-ming Burns Institute, First Hospital Affiliated to the General Hospital of People’s Liberation Army, Beijing 100037, China; JIA Xiao-ming Burns Institute, First Hospital Affiliated to the General Hospital of People’s Liberation Army, Beijing 100037, China; LI Li-gen Burns Institute, First Hospital Affiliated to the General Hospital of People’s Liberation Army, Beijing 100037, China; CAO Wei-hong Burns Institute, First Hospital Affiliated to the General Hospital of People’s Liberation Army, Beijing 100037, China; HAO Dai-feng Burns Institute, First Hospital Affiliated to the General Hospital of People’s Liberation Army, Beijing 100037, China; SHEN Chuan-an Burns Institute, First Hospital Affiliated to the General Hospital of People’s Liberation Army, Beijing 100037, China; TUO Xiao-ye Burns Institute, First Hospital Affiliated to the General Hospital of People’s Liberation Army, Beijing 100037, China; LIANG Li-ming Burns Institute, First Hospital Affiliated to the General Hospital of People’s Liberation Army, Beijing 100037, China; WANG Shu-jun Burns Institute, First Hospital Affiliated to the General Hospital of People’s Liberation Army, Beijing 100037, China

Correspondence to: CHAI Jia-ke  Burns Institute, First Hospital Affiliated to the General Hospital of People’s Liberation Army, Beijing 100037, China  (Tel:86-10-68989181 Fax:86-10-68989181 Email:cjk304@sohu.com )
This study was supported by : Eleven-fifth Research Fund of PLA(No. 06Z054)
Keywords: burn-blast combined injury·treatment
Abstract:

Background  Severe burn-blast combined injury is a great challenge to medical teams for its high mortality. The aim of this study was to elucidate the clinical characteristics of the injury and to present our clinical experiences on the treatment of such cases.
Methods  Five patients with severe burn-blast combined injuries were admitted to our hospital 77 hours post-injury on June 7, 2005. The burn extent ranged from 80% to 97% (89.6%±7.2%) of TBSA (full-thickness burns 75%–92% (83.4%±7.3%)). All the patients were diagnosed as having blast injury and moderate or severe inhalation injury. Functions of the heart, liver, kidney, lung, pancreas and coagulation were observed. Autopsy samples of the heart, liver, and lungs were taken from the deceased. Comprehensive measures were taken during the treatment, including protection of organ dys function, use of antibiotics, early anticoagulant treatment, early closure of burn wounds, etc. All the data were analyzed statistically with t test.
Results  One patient died of septic shock 23 hours after admission (four days after injury), the others survived. Dysfunction of the heart, liver, lungs, pancreas, and coagulation were found in all the patients on admission, and the functions were ameliorated after appropriate treatments.
Conclusions  Burn-blast combined injury may cause multiple organ dysfunctions, especially coagulopathy. Proper judgment of patients’ condition, energetic anticoagulant treatment, early closure of burn wounds, rational use of antibiotics, nutritional support, intensive insulin treatment, timely and effective support and protection of organ function are the most important contributory factors in successful treatment of burn-blast combined injuries.


 2007;120(20):1783-1787
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Burn-blast combined injury, which is caused by thermal energy and shock waves, has the symptoms of both the burned patients and the patients with blast injury. Such an injury should be approached as any major traumatic injuries, and the patients' condition should be scrutinized regularly for resuscitation and definitive care of the internal organs.1 Intensive attention should be given to such patients, owing to the high incidence of complications and mortality. On 7 June 2005, five patients with severe burn-blast combined injuries were admitted to our hospital, their clinical characteristics and the therapeutic strategies were summed up as follows.

METHODS

Patients
The five patients (all were males with a mean age of 24.6±2.4 years) were admitted to our hospital on 7 June, 2005 after being injured in an accident of explosion caused by 400 kg black dynamite (the explosion radius was 30 m and the patients were 10 m away from the explosion center). The extent of burn injury (TBSA) ranged from 80% to 97% (89.6%±7.2%), and the IIo, IIIo, and IVo burn accounted for 4%, 75%-92% (83.4%±7.3%), and 2%-9% (5.4±3.6%) respectively. On admission, all the patients had received a tracheostomy because of moderate and severe inhalation injuries (Table 1).


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Table 1. Extent and outcomes of burn-blast combined injury

Examinations
Blood samples from the patients were taken at 1, 3, 7, 14, 21, 28, and 35 days after the admission. Serum alanine aminotransferase (ALT), blood urea nitrogen (BUN), Mb isoenzyme of creatine kinase (CK-MB), atrial natriuretic peptide (ANP), total bilirubin (Tbil), amylase (AMY), and lipase were measured with a Monarch biochemical autoanalyzer (Hitachi, 7170, Japan). The changes in platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen concentration (Fib-c), and D-dimer (D-D) were also measured respectively.

Samples of the heart, liver, and lungs were taken immediately from the dead patient with the consent of his relatives. The tissues were fixed in 10% neutral buffered formalin, embedded in paraffin, sectioned in a thickness of 4 to 6 μm, stained with hematoxylin and eosin, and then observed under a light microscope (×400 HP). The blood monocytes were separated from the venous blood collected at 1, 3, 7, 14, 21, 28, and 35 days after admission to determine the expression of HLA-DR on CD14+ monocytes using monoclonal antibody staining and flow cytometry (BD Co., USA).

Statistical analysis
Data are presented as mean ± standard deviation (SD). By Stata 4.0, the data collected on and after admission were compared using paired t test. A P<0.05 was considered significant.

RESULTS

Clinical and laboratory findings
Four patients had a fever (>38.0˚C) on admission, and one showed hypothermia. All the patients had received a tracheostomy before admission and had decompression incisions of burn eschar on the extremities. Low PLT was found in all of them. PT was prolonged, and Fib-c and D-D levels were remarkably increased (Table 2). Plasma protamine paracoagulation test was positive on admission in two of the patients.


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Table 2. Changes in parameters of blood coagulation (mean ± SD)

In the patients, respiratory rate ranged from 20 - 35/min on admission, fibrobronchoscopy revealed hyperemia and edema of the tracheal mucosa without exfoliation of necrotic mucosa. Although the mucosal injury of the airway was not serious, abnormal PaO2 and PaCO2 (PaO2 < 60 mmHg, PaCO2 > 45 mmHg) were found in two patients, whose respiratory rate > 35/min. Assisted ventilation was given if the levels of SpO2 and PaO2 were lower than 90% and 60 mmHg respectively even when the volume of oxygen was increased to 10 L/min through tracheostomy tube. Patchy ground-glass shadows were found on chest X-ray films (Figs. 1-3). Bullae in the middle lobe of the right lung and right pneumothorax were found in one patient (Fig. 4). Pleural effusion was found bilaterally by B ultrasonography in all the patients.

The expression of HLA-DR on blood CD14+ monocytes on day 1 (38.15%±15.63%) was significantly lower than the normal (71.25%±10.56%, P<0.01), and then decreased sharply on day 28 (23.31%±14.34%).

On admission, all the patients showed tachycardia (104 - 146 beats/min). The CK-MB increased during day 1 to 3, and then decreased gradually. and the ANP was remarkably abnormal during days 1-7 in all the patients. One patient had a small amount of tricuspid regurgitation as shown by color ultrasonography. The levels of ALT and Tbil were persistently higher than the normal from day 5 to 35. Although there were no significant changes in BUN and Cr during the whole course, persistent hematuria and proteinuria were found from day 1 to 28. The levels of amylase in blood and urine, and blood lipase were significantly increased on day 1 to 5 (Table 3). Weak bowel sound and abdominal distention were found in all the patients on day 1 to 5.


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Table 3. Changes of multiple organ functions after admission (mean ± SD)

Outcomes
Four of the five patients survived, the other (96% TBSA), who had compound comminuted fracture of the left leg, with exposure of the upper left tibia and moderate inhalation injury, died of septic shock 23 hours after the admission. The pathological results of the lung, heart, and liver of the died patient are shown in Figs. 5-7.
 

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Fig. 1. In case 1, chest x-ray showing increased striated shadows in both the upper lungs.
Fig. 2. In case 3, chest x-ray showing patchy ground-glass shadows in the left lung.
Fig. 3. In case 4, chest x-ray showing patchy ground-glass shadows in both the upper lungs.
Fig. 4. In case 5, chest x-ray showing bullae in the upper lobe of the right lung and right pneumothorax.
Fig. 5. In case 2, who died after the admission, diffuse alveolar edema with pink fluid and patchy bleeding in both the lungs. Hyaline membrane, heavy infiltration of red cells and siderocytes, severe interstitial edema, and vasodilalation with stagnation of blood can be observed in some regions. (HE, original magnification ×400)
Fig. 6. Fragmentation and focal coagulation necrosis of myocardial fibers can be found in the right ventricle, and interstitial congestion and edema are observed (HE, original magnification×400).
Fig. 7. Pare faction of cytoplasm, fatty degeneration, bile pigment deposition in cytoplasm, dilatation of liver sinusoid, proliferation of Kupffer cells, and chronic inflammatory cell infiltration in the portal area can be observed in the liver (HE, original magnification×400).

DISCUSSION

Clinical characteristics of burn-blast combined injury
In patients with burn-blast combined injury, which is caused by thermal energy and shock waves, massive burn could induce a cascade of complications, including stress ulceration, systemic inflammatory reaction, sepsis, and even multiple organ dysfunction syndrome; in addition, shock wave produced by a strong detonation of explosives may cause further injury to the parenchymatous and hollow organs.2-6

Besides skin burns, severe dysfunction of the heart, liver, lungs, pancreas, and coagulation occurs early and lasted for a rather long time in the patients with burn-blast combined injuries. In our patients, hypotension with unknown reasons, showing decreased response to vasoactive drugs, was observed in 2 during the treatment; and assisted ventilation was performed in 3 because of dyspnea and hypoxemia on admission (2) or repeated attacks of dyspnea (1). Dysfunction of the liver developed early after admission and recuperated quite slowly. The pathological results in the dead patient show that the lungs, liver, and heart were all damaged severely after a burn-blast combined injury. In the survived patients, different degrees of pleural effusion were found, and two of them had ascites. In two patients, fibrobronchoscopy revealed mucosal congestion and edema, and chest X-ray demonstrated high density and ground-glass shadows, indicating that the injuries were not only produced by smoke or flame inhalation, but also by blast wave.

In all of our patients, signs of hypercoagulability were found on admission. Plasma protamine paracoagulation test was positive in two patients, who had significant changes of coagulation function. The expression of HLA-DR on CD14+ monocytes was remarkably decreased in all the patients, indicating long-term immunodeficiency. In the dead patient, the expression of HLA-DR on monocytes was only 35.79% on admission, while the normal value should be 71.25%±10.56%.

On account of the complicated pathological conditions involved in burn-blast combined injury, it seemed to be even more important to enhance the stamina of patients to the operative assaults, since there are mutiple injuries to organs and systems. All the derangements should be corrected as much as possible to enable the patients to withstand the surgical interventions.

Therapeutic strategies
In this series, the five patients were transferred to our department 77 hours after they had been preliminarily treated in other hospitals. Based on the characteristics of burn-blast combined injury, the following measures were taken immediately.

First of all, we protected and improved the organ functions and treated life-threatening complications immediately. Homeostasis was restored and maintained by correcting severe hypoproteinemia, acid-base imbalance, and electrolyte disturbance. Diffuse intravascular coagulation was prevented by using low molecular weight heparin (5000 U × 2-4 times/d) in patients with positive plasma protamine paracoagulation test and abnormal coagulation state.7 In the patients with a tendency of bleeding, prothrombin complex, fibrinogen, and platelets were used to enhance coagulation capability, then vitamin K1 was injected as well. A large dose of ulinastatin (600 000 U × 4 times/d) was used to suppress inflammatory response and the effects of leaked pancreatic enzymes.8 Cardiac tonics, including lanatoside C and 1, 6-phosphofructose, were used to improve the heart function, while reduced glutathione and glucuronlactone, etc., were used to protect the liver function. H2-receptor blocking agents and proton pump inhibitors were used to inhibit gastric acid secretion to prevent stress ulcer. Two of our patients with respiratory failure received protective assisted ventilation to reduce ventilation-associated lung injury, with the inspiratory pressure controlled at 30-35 cmH2O, tidal volume 6-8 ml/kg, and PEEP <15 cmH2O, a permissible hypercapnia was maintained as well.8 Since the patients had blast injury and inhalation injury, fibrobronchoscopy was performed to identify the extent of inhalation injury, and frequent tracheobronchial toilet and moistening of the airway by nebulization were used to prevent lung infection.

Early removal of burn eschar and closure of the burn wound were then carried out as soon as possible to prevent serious complications and aggravated organ dysfunctions subsequent to blast injury. 7,9 Escharectomy followed by mixed allogeneic and autologous micro-skin grafting was performed on the extremities or other parts of the body at 12 to 16 hours after admission. The mean extent of each excision was 55%±8% of TBSA. During and after the operation, the vital signs of the patients were relatively stable, and the main risk factor of patho- physiological changes in the later stages of burn injury were eliminated laying a foundation for the correction of existing morbid condition.

After the operations, antibiotics and immunotherapy were used to prevent and treat infections and sepsis. In our series, the persistent low level of HLA-DR expression on CD14+ monocytes suggested immunodeficiency, implicating a high risk of infection and sepsis.9-11 Special attentions should be given to such conditions, and full range immunotherapy, including immunoglobulin, panaxan, and thymic peptide, must be administered to the patients. Considering the immunosuppression in the patients, broad-spectrum antibiotics were used for the prophylaxis and control of infection before we obtained the results of culture of patients' excretion or blood, and then the doses of the antibiotics were adjusted timely according to the results of bacterial culture and the sensitivity tests. Prophylaxis of fungus infection was also important, especially in the patients with long-term use of antibiotics. In addition, Swan-Ganz catheter, indwelling venous lines, or urethral catheters should be retained as short as possible to reduce the incidence of iatrogenic infections.12-14

Nutritional support and regulation of metabolism are also very important for the patients. The body's response to burn injury is characterized by extensive changes in metabolism. Metabolic responses, including increased basal metabolic rate, nitrogen metabolism, and proteolysis,15-17 lead to increased energy expenditure and futile substrate cycling, resulting in depletion of nutritional and functional fat and protein stores, ending in a breakdown of functional structural proteins and organ dysfunctions.18-20 Therefore, nutritional surveillance and sufficient supplementation are imperative for accelerating patients' rehabilitation and reducing incidence of complications. In our patients, cardio-respiratory diagnostic system (Medical Graphics Co., USA) was used to monitor the resting energy expenditures, which is helpful for modulating required amount for each patient to meet his daily caloric requirements. In the early stage (within 7 days after injury), parenteral nutritional supply plays a key role in providing adequate nutrients for the patients; 7-10 days after injury, enteral feeding gradually becomes the main route to supply nutrients. However, a duodenal feeding tube should be inserted immediately on admission for enteral feeding. Moreover, fluid nutrients (Fresubin, 1.5 Kcal/ml) should be introduced to the patients continuously with a micro-pump to assure that they can tolerate the feeding, and recombinant human growth hormone (0.2 IU/kg/d) can be used to accelerate protein synthesis and wound healing in the late stage. Blood sugar level must be strictly controlled within 5-8 mmol/L by giving insulin intravenously via a micro-pump.21-24

Constant evaluation of patient's condition is necessary for modification of therapy. The morbid condition of patients with severe burn-blast combined injury maybe insidious because of the existence of blast injury. Obvious symptoms and signs might not be found till severe complications appeared. Thus, constant evaluation may help to detect the changes of patients' condition timely, so that appropriate alterations in the therapeutic measures can be taken immediately.25-27

Since the condition of the patients with burn-blast combined injuries is more complicated than that in burned patients, consultation of medical experts of different disciplines may contribute to correct diagnosis and perfection of treatment strategy.

Finally, we would like to stress the importance of psychotherapy for mental depression in the patients with massive burns, who have to face the intractable symptoms, and a long-drawn course of recovery.28-31 Therefore, psychotherapy, including brief psychological counseling and musicotherapy, should be carried out soon after admission. It is often helpful to give reassurance that suffering could diminish on its own, particularly if the patient has no premorbid history of depression or anxiety. In addition, drugs, such as oryzanol, may also be necessary to help patients sleep.

In conclusion, burn-blast combined injury may cause multiple organ dysfunctions, especially coagulopathy. Proper judgment of patients' condition, energetic anticoagulant treatment, early closure of burn wounds, rational use of antibiotics, nutritional support, intensive insulin treatment, timely and effective support and protection of organ functions are the most important contributory factors in successful treatment of burn-blast combined injuries

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