Esophageal echo-Doppler monitoring in burn shock resuscitation: are hemodynamic variables the critical standard guiding fluid therapy?

BACKGROUND: Ever since the introduction of invasive hemodynamic monitoring to major burn care, its utility remains controversial. Besides complications, invasive monitoring as a guideline for burn shock resuscitation is often associated with significant excessive fluid burden. This study was to summarize the clinical experiences of noninvasive esophageal echo-Doppler (ED) monitoring in burn shock resuscitation and discuss the significance of hemodynamic variables in assessment of fluid therapeutic goal. METHODS: Twenty-one burn patients with an average total body surface area of 78.86% +/- 7.75% (62-92%) was enrolled in this retrospective study. Fluid therapy was guided according to Chinese general formula and adjusted with urinary output 1 mL/kg/hr as resuscitation goal. Hemodynamic parameters using ED was obtained, including cardiac output (CO), stroke volume (SV), myocardial contractility parameter--maximum acceleration at onset of systole (Acc), afterload parameter--total systemic vascular resistance (TSVR), preload parameter SV/Acc. RESULTS: All patients were clinically diagnosed with a relatively stable condition during early shock stage. There existed inherent and dynamic tendency of hemodynamics during burn shock resuscitation with low CO, Acc, SV/Acc, and high TSVR at first followed by a continuous trend of increase in CO, Acc and SV/Acc and decrease in TSVR. Significant correlations could be seen between CO and Acc, CO and TSVR, CO and SV/Acc. The Standardized Regression Coefficients of Acc, TSVR, and SV/Acc with CO as dependent variable were 0.343, -0.670, and 0.053, respectively demonstrating that myocardial contractility and angiotasis played more important role than blood volume did in hemodynamic variation. CONCLUSIONS: Hemodynamic variables cannot routinely substitute traditional variables as the burn shock resuscitation goal. Because of its noninvasiveness, ability to real-timely provide complete profile of hemodynamics, ED monitoring is a good adjunctive method for clinical judgment.

[Role of c-Jun NH (2)-terminal kinase in insulin resistance after burn].

OBJECTIVE: To investigate the role of c-Jun NH (2)-terminal kinase (JNk) in insulin resistance after burn and its mechanism. METHODS: Twenty-four Sprague-Dawley rats were randomized to control, burn and burn + anisomycin groups. The rats in control group received sham burn trauma, and burn and burn + anisomycin groups received 30% total body surface area (TBSA) full thickness burn injury. Anisomycin (5 mg/kg) together with 250 microl dimethyl sulfoxide (DMSO) was injected to the rats in anisomycin group intravenously, and only 250 microl DMSO in the other two groups. Euglycemic-hyperinsulinemic glucose clamps was performed 2 hours after the injection. The changes of phospho-serine 307, phospho-tyrosine of insulin receptor substrate (IRS)-1 and phospho-JNK in muscle tissues were determined and compared using immunoprecipitation and Western blot analysis or immunohistochemistry in the three groups. RESULTS: The infusing rates of total 10% glucose (mg x kg(-1) x min(-1)) in control, burn and burn + anisomycin group were 12.3 +/- 0.4, 6.6 +/- 0.3, 6.5 +/- 0.4, respectively. The level of IRS-1 Serine 307 phosphorylation and phospho-JNK in muscle increased significantly, while insulin-induced tyrosine phosphorylation of IRS-1 decreased markedly after burn. CONCLUSIONS: The activation of JNK elevates the level of IRS-1 phospho-serine 307 and might play a role in insulin resistance after burn in rats.

[Amelioration of insulin resistance after scald by c-Jun N-terminal kinase inhibitor in rat].

OBJECTIVE: To investigate the role and mechanism of c-Jun N-terminal kinase (JNk) inhibitor (SP600125) in amelioration of insulin resistance after scald. METHODS: Twenty-four Sprague-Dawley rats were randomized into sham (the process of scald was mimicked by water at room temperature) , scald, scald and SP600125 groups. The rats were inflicted with 30% TBSA full-thickness scald in the latter two groups. Euglycemic-hyperinsulinemic glucose clamp experiment was carried out 4 days after scald. SP600125 was administered to the rats in scald and SP600125 2 hrs before Euglycemic-hyperinsulinemic glucose clamp was performed. Changes in the phospho-Serine307 and phospho-tyrosine of IRS-1 activity, as well as expression of phospho-JNK in muscles were determined. RESULTS: Euglycemic-Hyperinsulinemic Glucose Clamps experiment showed that the infusion rate of 100 g/L glucose in sham, scald, scald and SP600125 groups were (12. 33 +/-0. 42) , (6. 61 +/-0. 27) , (11. 11 +/-0. 68) mgx kg(-1) x min(-1) , respectively ( P <0.01). The level of IRS-1 Serine307 phosphorylation and JNK activity in muscles were significantly increased, while insulin-induced tyrosine phosphorylation of IRS-1 decreased markedly after scald. Compared with scald group, the level of IRS-1 Serine307 phosphorylation and JNK activity in scald and SP600125 group were decreased but tyrosine phosphorylation was elevated. CONCLUSION: SP600125 can partially ameliorate insulin resistance after scald by inhibition of JNK activation, and decrease the level of IRS-1 phospho-serine307.

[Changes of myocardial dynamics in early stage of burn and effect of rapid fluid replacement in delayed resuscitation].

OBJECTIVE: To investigate the changes in myocardial dynamics in early phases of burn shock of dogs and the effects of rapid fluid infusion in delayed resuscitation. METHODS: Twelve mongrel dogs were randomly divided into control (n=6) and burn (n=6) groups. The dogs in burn group were subjected to 35% total body surface area (TBSA) III degree burn and were resuscitated with lactate Ringer's solution 6 hours postburn. The volumes and rates of fluid infusion were controlled basically on the urinary output of 1.0 mlxkg(-1)xh(-1) and cardiac output (CO) of 70%-80% of pre-burn values. The mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), maximum rate of intraventricular pressure rise/down (+/-dp/dt max) and cardiac index (CI) were determined at 0.5, 1,2, 6, 7, 8, 10 and 24 hours postburn. RESULTS: The MAP, LVSP, +/-dp/dt max and CI were significantly lowered from their baseline and those of control group at 0.5 hour postburn, and they kept declining until 6 hours postburn. They showed a tendency of elevation and reached or approached the levels of that in control group within 2 hours of resuscitation, and the differences were not significant between the two groups 4 hours after burn (all P>0.05). The amount of infusion fluid within the first 4 hours of resuscitation was (3.63+/-0.99) ml/kg per 1% TBSA. CONCLUSION: The myocardial dynamics is depressed in the early stage of burn, the effective way to improve it is to infuse a large amount of fluid rapidly when resuscitation is delayed.

[Experimental study of human skin fibroblasts cultured in three-dimension(3D)].

OBJECTIVE: To investigate the biological characters of human skin fibroblasts in fibroblast populated collagen lattice (FPCL). METHODS: The human fibroblasts were cultured in 3D and the collagen of the rat tail was also prepared. They were examined with the comprising cell cycle and apoptosis, mRNA expression of TGF beta1, and fibronectin, and cell morphology. RESULTS: The flow cytometry showed that the G0/G1, stage cells were 79% +/- 3%, 87% +/- 2% after the 7 days and 14 days separately, and there were not apoptosis peak observed. RT-PCR analysis revealed that the mRNA expression of TGF beta1, and fibronectin had no difference between human skin fibroblasts cultured in 3D and 2D. Electron microscope showed the cells were plenty of chromatin and organelles. CONCLUSIONS: The proliferation of the human skin fibroblasts in FPCL is slow, but its biological viability is better.

[Clinical observation of the long-term effects of rhEGF on deep partial-thickness burn wounds].

OBJECTIVE: To evaluate the safety and long-term effect of recombinant human epithelial growth factor (rhEGF) on deep partial-thickness burn wounds. METHODS: Thirty-seven burn patients were enrolled in this study and were observed by randomized, double-blinded and placebo-controlled protocol. An area of deep partial-thickness burn wounds from each patient was divided into control (C) and treatment (T) portions. The wound in C was treated with normal saline while that in T with rhEGF. The patients were followed-up for 1 and 4 years after wound healing. The healed wounds were evaluated by modified Vancouver scar scale in terms of scar index (SI). RESULTS: 1 year after wound healing, it was found that the SI in T group (7.19 +/- 1.67) was obviously lower than that in C group (8.92 +/- 1.78, P < 0.01). The SI in T group (6.12 +/- 1.54) was still evidently lower than that in C group (8.09 +/- 1.81, P < 0.01) four years after wound healing. There were no signs of development of tumor or cancer in all the tested burn wound areas. CONCLUSION: External application of rhEGF might be beneficial to the healing quality of deep partial-thickness burn wound with less scar formation and better long-term effects, and it is safe.

[Inhibition of nimodipine on production of proinflammatory by Kupffer cells in severe burned rats].

OBJECTIVE: To study whether nimodipine, a dihydropyridine-type calcium channel blocker, can inhibit the production of interleukin-1beta(IL-1beta), interleukin-6(IL-6) by Kupffer cells(KC) and down-regulate its level of plasma after severe burn injury. METHODS: KC of normal rats were isolated with portal vein catheter, intrahepatic digestion and density gradient centrifugation. Intracellular calcium concentration ([Ca2+]i) in individual KC after stimulated with postburn serum was assessed fluorometrically with microspectrofluorimeter. Level of IL-1beta and IL-6 in the supernatant of KC cultured with postburn serum were detected by enzyme-linked immunosorbent assay(ELISA). SD rats underwent 30% total body surface area(TBSA) full thickness burn 6 hours later, KCs was isolated and their mRNA were extracted. Level of IL-1beta mRNA and IL-6 mRNA were detected by ribonuclease protection assay(RPA). Levels of plasma IL-1beta and IL-6 were also detected. Role of nimodipine on above-mentioned effects were observed. RESULTS: Compared with that of control group, levels of [Ca2+]i of KCs and IL-1beta and IL-6 supernatant in burn group increased significantly(all P<0.01). At present of 1 micromol/L nimodipine, however, the [Ca2+]i, IL-1beta, IL-6 values decreased significantly(all P<0.01). The level of plasma cytokines and KC mRNA in burn group also increased significantly. After intravenously injection with nimodipine (40 microg x kg(-1) x h(-1)), the numerical values decreased significantly(all P<0.01). CONCLUSION: Kupffer cells of rats are activated to secret IL-1beta and IL-6 after severe burn injury and this process is realized through calcium ion signal transduction channel. Nimodipine can inhibit IL-1beta and IL-6 production of KC by preventing its mRNA transcription, down-regulating its level of plasma.

Effect of burn injury on relative anaplerosis and gluconeogenesis in rats by 13C magnetic resonance spectrum.

OBJECTIVE: To introduce a safe and specific approach of (13)C magnetic resonance spectrum ((13)C MRS) spectroscopy and investigate the alterations in hepatic anabolism. METHODS: Relative anaplerotic, pyruvate recycling and gluconeogenic fluxes were measured by (13)C MRS isotopomer analysis of blood glucose from rats with 40% body surface area burn injury, and from rats exposed to sham injury. A short chain fatty acid, [U (13)C] propionate which was avidly extracted by the liver, was infused intravenously to deliver (13)C into the citric acid cycle. Proton-decoupled (13)C MRS of deproteinized plasma or extracts of the freeze-clamped liver were used to determine the distribution of (13)C in blood or hepatic glucose. RESULTS: There was no difference in the multiplets detected in the glucose carbon-2 anomer from blood or liver after 45 or 60 minutes of the infusion of the propionate, indicating that steady-state isotopic conditions were achieved. Gluconeogenesis relative to citric acid cycle flux was not altered by burn injury; in both sham and burn groups the rate of glucose production was about equal to flux through citrate synthase. In the sham group of animals, the rate of entry of carbon skeletons into the citric acid cycle was about 4 times than that in the burn group. Similarly, flux through pyruvate kinase (again relative to citrate synthase) was significantly increased after the burn injury. CONCLUSIONS: Since results from analysis of the blood glucose are the same as that of the hepatic glucose, (13)C distribution in the glucose and hepatic metabolism can be assessed based on the (13)C MRS analysis of the blood glucose.

[Study on the intra- and extra-hepatocyte distribution of sodium ions in scalded rats during early postburn stage].

OBJECTIVE: To investigate the characteristics of the intra- and extra-hepatocyte sodium ions distribution in scalded rats during early postburn stage,with the aim of improving burn shock resuscitation regime and the resuscitation effects. METHODS: Adult Sprague-Dawley rats were randomly divided into sham scalding (C, n = 12) and scalding (S, n = 7) groups. The rats in S group were subjected to 40% TBSA III degree scalding on the back and were catheterized via jugular vein for fluid resuscitation. The rats in C group were catheterized via jugular vein without fluid infusion and were sham scalded by warm water in temperature of 37 degrees. The changes in the intra- and extra-hepatocyte sodium ion contents were determined in vivo by (23)Na-magnetic resonance spectrum technology, while the existing state of the intra- and extra-hepatocyte sodium ion was determined by detecting (23)Na-magnetic resonance horizontal delaying time (T(2)). RESULTS: The extra-hepatocyte sodium content in S group at 24 postburn hours (PBHs) was 17% less than that in C group. In addition, the T(2f) (fast T(2)) in S group remained stable but maintained a higher ratio during the observation time. This suggested that the sodium binding sites in extra-hepatocyte matrix increased relatively and that intra-hepatocyte sodium content increased by 57%. But the T(2) and the fast and slow parts of the T(2) kept stable, which implied that intra-hepatocyte catabolizing products were increased. This led to an increase in the sodium ion binding sites within intra-hepatocyte matrix in proportion to the sodium ion content. CONCLUSION: During early postburn stage, the extra-hepatocyte sodium in a remote organ such as the liver exhibited relative deficiency due to its ingress into hepatocyte cytoplasm and to the increase of sodium combining sites.

[The role of Kupffer cells on the postburn production of TNFalpha, IL-1beta and IL-6 in severely scalded rats].

OBJECTIVE: To observe the role of Kupffer cells in the postburn production of TNFalpha, IL-1beta and IL-6 in severely scalded rats. METHODS: (1) The production of TNFalpha, IL-1beta and IL-6 from rat Kupffer cells stimulated by burn serum was observed. (2) The postburn change in the expression of cytokine mRNA from rat Kupffer cells was monitored. (3) The change in the plasma cytokine contents in scalded rats was determined after the application of gadolinium chloride, a specific inhibitor of Kupffer cells. RESULTS: Kupffer cells could be stimulated by burn serum to release cytokines TNFalpha, IL-1beta and IL-6. The mRNA expression of TNFalpha, IL-1beta and IL-6 from rat Kupffer cells increased significantly after injury. But the postburn plasma levels of TNFalpha, IL-1beta and IL-6 decreased obviously to 34.71%, 36.99% and 33.7% of those in scalding group, respectively, after the Kupffer cell activity was inhibited. CONCLUSION: The plasma cytokines, i.e. TNFalpha, IL-1beta and IL-6, were primarily produced from Kupffer cells after injury in scalded rats, initiated by TNFalpha, IL-1beta and IL-6 mRNA transcription.