| Background:Nutritional support is an important method in the treatment of trauma and sepsis patients. However, implementation of nutritional support often results in no satisfactory results due to its complicated co-morbility. Up to40%of ICU patients experience various degrees of malnutrition. The cause of malnutrition is closely related to inadequate energy supply. Both nutrition underfeeding and overfeeding could result in malnutrition. Underfeeding could lower immunological function, prolong wound recovery and increase nosocomial infectious morbidity; while overfeeding aggravates the burdens of organ, and increases the likelihood of steatosis, hyperlipidemia, hyperglycemia, low hypophosphatemia, and impairs immune function. Either underfeeding or overfeeding could prolong hospitalization, mechanical ventilation duration and raise associated complications. Appropriate nutritional support can improve prognosis, immunity, and reduce complications. But how to provide proper nutritional support is a debated issue which still lacks effective clinical standard. The lacking of clinically developed uniform standards to optimize patient’s nutritional state contributes to malnutrition. Therefore, setting an optimal nutrition standard for patients is vital.Indirect calorimetry (IC) is based on the energy conservation law of geometric theorems and monitor chemical reactions in energy metabolism. Through the consumption of carbohydrates, fat and proteins, the human body will produce heat, consume a certain amount of oxygen and produce a certain amount of carbon dioxide. According to this principle, by measuring the consumption of oxygen (VO2) and the release of carbon dioxide (CO2) in a preset time, with the Weir equation, the energy consumption could be calculated and the energy consumption of24hours could be speculated. To date, IC is considered as the golden standard in measuring resting energy expenditure, however, the application of IC in determining the optimal nutrition standard still lacks global similar prospective randomized controlled trials with positive results to support the hypothesis to use resting energy expenditure to determine the target energy.With regards to setting optimal nutritional standard for critically ill patients, Europe (ESPEN) and the U.S.(ASPEN) guidelines recommend measuring resting energy expenditure (MREE) to derive the optimal nutritional state, and also using weight and energy metabolism estimation formula to calculate the target energy state, these recommended approaches relies mainly on the consensus of experts, supported by the lack of evidence-basedDuring and post trauma and sepsis, the human body will release a series of cytokines, and also experience in different degrees of increase in terms of oxygen consumption, Proteolysis, Cardiac output, Glucocorticoid and Catecholamine. The Utilization and synthesis of nutrients also changed, the traditional nutritional support could not offset the increase in catabolism and protein loss. Some cytokines such as TNF-a, IL-2, IL-6involved in the regulation of inflammatory reactions, the IL-6protein will induce the liver to prioritize the synthesis of Acute phase proteins (such as the C-reactive protein), thus Albumin, Pre-albumin, Transferrin and Immunoglobulin concentration decreases. The change of Pro-inflammatory cytokines and lower metabolism are associated with mortality.Objective: Primary endpoints:To observe the effect of different target energy value on prognosis. IC was utilized to measure changes in resting metabolic rate to provide different levels of energy supply. The effect of different caloric supply on28day,60day mortality rate of trauma and sepsis patients was observed. Which level of caloric supply is the most suitable for Critical patients were analyzed, so as to provide a more accurate strategy to instruct the clinical nutritional support implementation.Secondary endpoints:1. To observe the resting energy expenditure characteristic related to trauma, sepsis patients, to perform the consistency analysis between our value and predicted formula and to discuss the related factors of resting metabolic rate.2. To observe the impact of different caloric supplement levels on the mechanical ventilation and ventilation-free days of trauma and sepsis patients.3. To observe the impact of different caloric supplement levels on the nutritional indicators, liver function, inflammatory indicators, immune function and inflammatory cytokines in trauma and sepsis patients.Methods:Part1:The characteristic, monitoring and evaluation of resting energy metabolism in trauma and sepsis patients.Patients with sepsis and trauma (including post-surgery) were included from2011/6/1to2013/12/31admitted to the ICU of Guangdong Armed policed Hospital. The characteristics of patients were recorded and the resting metabolic energy value was measured. The values of resting energy metabolism in various formulas were calculated. The bias analysis between the measured resting energy metabolism value and calculated formula value were performed and the accuracy was compared; the energy distribution were analyzed and the consistency analysis between formula estimation data and the actual measuring value of the metabolic energy level were processed to evaluate the clinical acceptable ranges. The correlation analysis between the two approaches were also conducted.Part2:The impact on the outcome and complications under different target energy level in trauma and sepsis patients. 253cases of patients admitted to the ICU of Guangdong Armed policed Hospital were included from2011/6/1to2013/12/31and divided into four groups through randomization:group one used the ACCP formula of25kcal/kg/day as the target energy level; group two used the80-89%of the target energy level from the resting metabolic rate; group three using90-110%as target; group four using over110%. All patients were received conventional treatment, and enteral nutritional supports were administered within24hours under stable condition.4-5days were cost to achieve the target energy level, and if not, parenteral nutritional support was supplemented. Protein dosage is1.0g/kg/day. Daily support of energy level, protein level and administration method were recorded, along with administration time, accumulated energy balance weekly and the total energy balance when transferred out of ICU or out the hospital (deceased). The mortality rate on28day and60day, ICU stayed and total hospital stay, ventilation-free days within28day were recorded, and survival analysis of60day was performed. the APACHE II, SOFA score before treatment (day0), first day under treatment (day1), third day under treatment (day3), fifth day under treatment (day5), seventh day under treatment (day7) or after transfer out or discharge were calculated, and the pre-albumin, retinol binding protein, transferrin, liver function index level were detected before treatment (day0), seventh day under treatment (day7), tenth day under treatment (day10), fourteenth day under treatment (day14). Gauge the immune index(CD14+/HLA-DR) on before treatment (day0) and seventh day under treatment (day7).Part3:The impact of different target energy level on the inflammatory cytokine levels in trauma and sepsis patients.45cases of patients admitted to the ICU of Guangdong Armed police Hospital were included from2011/6/1to2013/12/31and were divided into the same four groups plus control group. The patients who enrolled in the control group were hospitalized during the same period without sepsis (APACHE II score<12). The characteristics were recorded, and the inflammatory cytokine levels (IL-6、IL-10、 TNF-α、IL-4) were measured on the day before nutritional support (day0) and seventh day under treatment (day7). The Pro-inflammatory/Anti-inflammatory balance (IL-6/IL-10、IL-10/TNF-a) was observed.Result:1. The characteristics, monitoring and assessment of resting energy metabolism in trauma and sepsis patient:1.1Comparison of measured resting energy metabolism values with other calculated formula values:The resting energy metabolism rate estimated by ACCP was not significantly different compared with indirect measuring values (t=1.534, P=0.126). Where other calculated formula values was significantly different(t=6.478、7.938, respectively and P<0.000) from indirect measuring value.1.2. The characteristic of resting energy metabolism:More than50%of trauma and sepsis patient manifested a hypermetabolic state, with22.22%-22.83%manifesting normal and the rest manifesting hypo-state. There was no significant difference among three groups (P>0.05).1.3. The correlations between indirect measurement and different calculated formula values:The majority of the calculated formula values had up to95%precision consistency in95%ranges, while ACCP and Ireton-Jones92formula indicated more than97%precision consistency. Due to the fact that large range outside the clinical acceptance, and±10%MREE (-195.46,195.46) kcal/day is more reasonable range, consistency analysis was re-performed, and the previous high precision were significant decreased with ACCP, H-B and Mifflin formula consistency of27.27%,27.67%and27.67%, respectively, and Ireton-Jones92consistency of18.18%.1.4Direct measurement correlation analysis:There was a significant correlation between various formula values and the direct measurement value (P<0.000), with Mifflin with r value of0.474to be strongest correlated and ACCP with r value at0.317to be weaker. While resting energy metabolism were positively correlated with body weight and BMI, and negatively correlated with NRS2002, and no correlation with APACHE II were observed (P=0.511). 2. The effect of different target energy levels on the prognosis and complications in sepsis and trauma patients.2.1The comparison of calorie and protein intake:There is a statistical significance in the initial week calorie intake in all groups (F=16.366,P=0.000).The average energy intake, the accumulative energy intake balance and the total energy balance during first week were much lower in group2than those of other three groups, while the average protein intake between the four groups during the first week were similar (F=2.028,P=0.110).2.2Various target energy on ICU stay and mechanical ventilation duration:There were no statistical significances of mechanical ventilation duration, ICU stay and total hospital stay in all groups (F value is0.543,0.896,1.481,P value is0.654,0.445,0.220,respectively), except for ventilation-free time within28day (F=2.763, P=0.043). The ventilation-free time within28day were much longer in90-110%and25kcal/kg group compare with the other two groups.2.3Comparison of the28-day,60-day mortality rate.The28-day mortality rate of the90-110%group (12.1%) was lower than the other three groups (>23.3%) with no significance. The60day mortality rate all increased, with90-110%group of21.5%and other three groups of more than40%, and the compassion was statistically significant (χ2=12.712,P=0.005).2.460-Day Kaplan-Meier Survivability Analysis:The60Day Kaplan-Meier analysis showed that the mortality rate was lower in90-110%group than those in other three groups, with statistical significance (χ2=10.375,P=0.016).2.5The changes of nutritional indexes pre and post treatment:With the pass of time, the level of Retinol binding protein raised gradually and significantly (F=10.126,P=0.000). The rise in80-89%group was not significant, while the other three groups observed remarkable increase. Transferrin and pre-albumin also rised significantly over time (F=4.611,P=0.016). While there was no difference among the4groups (F=0.411,P=0.868).2.6The changes in immune functions pre and post treatment: The CD14+/HLA-DR expressions in all groups were similar in first week (F=1.992, P=0.166) and increased significantly since second week (F=3.739,P=0.016) with the80-89%and90-110%group to be more distinct. Through analyzing the different nutritional support approaches, the CD14+/HLA-DR expressions in all groups changed little in first week, after one week of the treatment, the HLA-DR presentation was increased in EN group and mixed group combining EN and PN, while decreased in PN group, and the difference were statistically significant (F=6.612,P=0.003).3. The impact of different target energy level on inflammatory cytokines levels in sepsis and trauma patients.3.1The cytokine levels after treatment:There were significant differences in IL-4and IL-10levels after treatment across the groups (F=6.766,P=0.000,and F=4.479,P=0.004). The IL-4levels in80-89%group were much different from those in90-110%group and25kcal/kg group (P<0.05), and those in>110%group were significantly different from25kcal/kg group and90-110%group (P<0.05). There was no difference in IL-4levels in90-110%group and25kcal/kg group (P>0.05). The IL-10levels were similar in4groups (P>0.05) and higher than that in control group (P>0.05). The IL-6and TNF-a levels were similar in all groups (F=0.617,P=0.653vs F=2.363, P=0.070).3.2The inflammatory cytokine levels after treatment:The IL-6levels in90-110%group decreased after treatment (t=3.779,P=0.005), while other groups observed non statistical significances (P>0.05). The TNF-a and TL-10levels were similar in all groups (P>0.05). The IL-4levels only in80-89%group and90-110%group changed significantly (P<0.05).3.3IL-6/IL-10ratio:There were no significant differences in4groups (P>0.05), and the IL-6/IL-10ratio in treatment groups were significantly different than that in control group (F=12.489,P=0.000) before treatment. After treatment, the IL-6/IL-10ratio raised remarkably in the80-89%group (P<0.05), while decreased significantly in90-110%treatment group (P<0.05). 3.4IL-10/TNF-α ratio:There were no significant differences in4groups, and the IL-6/IL-10ratio in treatment group were significantly different than that in control group (F=57.084, P=0.000) before and after treatment. It raised remarkably in the control group(t=-4.746,P=0.01), while kept similar in other4treatment groups (P>0.05).3.5Correlation analysis of inflammatory cytokine levels:Prior to the treatment, the inflammatory cytokine’s level was positively correlated with APACHE Ⅱ score (P<0.000); and anti-inflammatory cytokine was negatively correlated with APACHEII score (P=0.009and P=0.000,respectively). Post nutritional support treatment, IL-6levels were negatively correlated with actual energy supply (P=0.041); while IL-10, IL-4and TNF-a levels were not (P>0.05).Conclusion:1. Trauma and sepsis patients experience different resting metabolic disorder at early stage, the formulas on calculating resting metabolic rate have certain bias from measured values. Under the clinical acceptable criteria, no consistency between measured value and formula calculated ones were unsatisfactory. The formula calculated value will result in over or underfeeding.2. Resting metabolic rate is negatively correlated to the nutritional condition admitted to the hospital, and is positively correlated to weight and BMI index.3. Different degrees of nutritional support have no impact on28days prognosis, while providing90-110%of the required caloric value will improve the survival rate at day60. And different degrees of nutritional support have no impact on patients’ mechanical ventilation duration, ICU stay or total hospital stay, but it affects ventilation-free time at28day. Providing90-110%of the required caloric value prolongs ventilation-free time at28day.4. Appropriate nutritional support could restore the pro-inflammatory/anti-inflammatory balance through reducing pro-inflammatory cytokines release, and have no effect on pro and anti-inflammation balance. |
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