Evaluation Of The Effect Of High-protein Supply On Diaphragm Atrophy In Critically Ill Patients Receiving Prolonged Mechanical Ventilation

BackgroundMechanical ventilation,as an important treatment method for patients with ventilating pump failure and gas exchange disorder,is widely used in ICU and has saved the lives of numerous patients with acute and chronic severe cardiopulmonary failure.Although most patients recover from the initial critical illness and easily wean from the ventilator,20%-30% of patients require delayed weaning and extubation.Respiratory muscles are the power pump of respiratory movement,and the diaphragm is the most important inspiratory muscle,accounting for 60%-80% of all respiratory muscle functions.Even if the mechanical ventilation is maintained for a short time,diaphragm fatigue may also occur due to atrophy or decreased contractile function,which is known as ventilator-induced diaphragm dysfunction.Thus,leading to prolong the length of hospital stay,long-term dysfunction,and an increased risk of death.Nutrition therapy is not only a support method for critically ill patients,but also an important treatment measure.Its importance has long been recognized.Many studies have evaluated that increasing the protein and energy available to patients in the ICU reduces infection and complications,shortens mechanical ventilation time,lowers patient mortality and improves long-term physical recovery.There has not been research on whether increased protein supply improved ventilator-induced diaphragmatic dysfunction.ObjectivesIn this study,diaphragmatic muscle content was innovatively observed through CT to directly evaluate diaphragm atrophy.The study aimed to evaluate the effect of high-protein supply(2.0 g/kg/day)on diaphragm atrophy,trophic metabolic status,and the prognosis of patients receiving prolonged mechanical ventilation in the ICU.It provides theoretical basis for nutritional support of patients with prolonged mechanical ventilation.MethodsBetween September 2017 and September 2019,critically ill patients with mechanical ventilation >7 days in the Geriatrics ICU of First Affiliated Hospital of Nanjing Medical University were enrolled and randomly assigned to the standard nutrition treatment(SNT)group(target calorie 25-30 kcal/kg/d,protein 1.2 g/kg/d)and intensive nutrition treatment(INT)group(target calorie 25-30 kcal/kg/d,protein 2.0 g/kg/d).1.Demographic data,body mass index(BMI),acute physiology and chronic health evaluation(APACHE II),sequential organ failure assessment(SOFA),nutrition risk screening 2002(NRS-2002),admission diagnosis,arterial blood gas,ventilator settings,tidal volume and actual nutrition implementation were prospectively recorded on the first day of mechanical ventilation.2.The enrolled patients underwent computer tomography within 24 hours before or after tracheal intubation.To calculate the volume of the costophrenic angle from the upper edge of the 11 th thoracic vertebra(T11)to the lower edge of the 1st lumbar vertebra(L1).CT was reviewed weekly according to the patient’s condition during the course of the illness until the patient weaned from the mechanical ventilation or died.The changes in percentage decreased in the diaphragm volume were compared between the two groups.(diaphragmatic muscle content in week 1-diaphragmatic muscle content in week n diaphragmatic muscle content in week 1×100%)3.Nitrogen balance(NB),prealbumin(PRE),and transferrin(TRF)were tested within 24 hours after tracheal intubation and were subsequently monitored weekly until the patient weaned from the mechanical ventilation or died.4.Blood samples were collected from the enrolled patients within 24 hours before tracheal intubation,followed by using ELISA to detect the butyrylcholinesterase(BCh E),TNF-α and IL-6.Patients were monitored weekly until they were transferred out of the ICU or died.5.The oxygenation index(partial pressure oxygen/inspired oxygen concentration),the partial pressure of carbon dioxide(Pa CO2),the Vt,the rapid shallow breathing index(respiratory rate/Vt,RSB),and the respiratory system compliance [Vt/(platform pressure-PEEP),Crs] of the patients were recorded weekly until the patient weaned from the mechanical ventilation or died.6.Weaning from mechanical ventilation,tracheotomy rate,duration of ventilation in ICU survivors,duration of ICU admission in ICU survivors and ICU mortality were compared between the two groups.Results41 patients found to meet the eligibility criteria,including 21 patients in the SNT group and 20 patients in the INT group.1.Demographic and clinical characteristics of the study populationAt baseline,participants in both groups were similar in terms of sex,age,BMI,APACHE II,SOFA and NRS-2002,admission category,ventilator settings,and blood gases.The actual protein intake(1.06±0.21 vs 1.70±0.21 g/kg/day,P < 0.001),calorie intake(25.75±4.81 vs 33.46±2.78 kcal/kg/day,P < 0.001),and time at which 80% of the prescription reached the target(5.24±2.28 vs 8.60±3.98 d,P=0.002)of the SNT group were significantly different from those of the INT group.2.Effect of INT on inflammatory factorsNo differences in TNF-α and IL-6 were found between the two groups of mechanically ventilated patients in the first 1–5 weeks.However,as the length of the hospitalization increased,both TNF-α and IL-6 were gradually reduced.Compared with the first week,TNF-α in SNT group showed an obvious decreased trend from second week(second week:61.79±48.40 vs 179.67±215.14 pg/ml,P=0.019;third week:65.93±63.15 vs 179.67±215.14 pg/ml,P=0.049;fourth week:44.09±26.70 vs 179.67±215.14 pg/ml,P=0.039;fifth week:32.98±18.88 vs 179.67±215.14 pg/ml,P=0.087).IL-6 also showed a decreased trend,and the difference was significant from the fourth week(second week: 334.80±544.37 vs 529.00±895.00 pg/ml,P=0.402;third week:164.37±159.33 vs 529.00±895.00 pg/ml,P=0.081;fourth week:72.02±64.79 vs 529.00±895.00 pg/ml,P=0.030;fifth week:39.41±20.26 vs 529.00±895.00 pg/ml,P=0.021).Compared with the first week,the level of TNF-α in INT group showed significant decreased from the second week(second week : 65.10±63.42 vs 187.64±213.98 pg/ml,P=0.019;third week:64.33±54.74 vs 187.64±213.98 pg/ml,P=0.027;fourth week:30.02±14.80 vs 187.64±213.98 pg/ml,P=0.010;fifth week:31.93±25.40 vs 187.64±213.98 pg/ml,P=0.024).The decrease in IL-6 levels from the second week was statistically significant compared with the first week(second week:266.02±273.07 vs 748.25±922.88 pg/ml,P=0.035;third week:90.49±71.81 vs 748.25±922.88 pg/ml,P=0.005;fourth week:50.15±40.14 vs 748.25±922.88 pg/ml,P=0.003;fifth week:45.99±37.72 vs 748.25±922.88 pg/ml,P=0.018).3.Effect of INT on metabolic stateThe two groups of patients had negative NB in the first 3 weeks of mechanical ventilation,showing no significant difference between groups(first week:-7.42±6.42 vs-9.30±6.92 g,P=0.380;second week:-6.55±5.77 vs-9.42±6.79 g,P=0.156;third week:-8.44±4.54 vs-8.10±7.54 g,P=0.869).In the fourth week,the negative NB of the INT group was significantly better than that of the SNT group(-1.66±5.82 vs-7.14±6.47 g,P=0.041).In the fifth week of mechanical ventilation,the patients in the INT protein group showed a positive NB and significant improvement,compared with the patients in the SNT group(1.85±0.90 vs-4.22±4.63 g,P=0.032).No significant difference in serum PRE levels was found between the two groups of critical patients receiving mechanical ventilation in the first week(0121±0.058 vs 0.128±0.050 g/L,P=0.701)and second week(0.139±0.072 vs 0.155±0.054 g/L,P=0.429).After the third week,the PRE levels of the INT group were significantly higher than those of the SNT group(third week: 0.185±0.040 vs 0.141±0.058 g/L,P=0.017,fourth week: 0.201±0.050 vs 0.143±0.053 g/L,P=0.015,fifth week: 0.270±0.082 vs 0.157±0.048 g/L,P=0.010).No significant difference in serum TRF between the two groups was found in the first 1–4 weeks(first week: 1.339±0.567 vs 1.431±0.592 g/L,P=0.613,second week: 1.221±0.565 vs 1.371±0.451 g/L,P=0.357,third week: 1.248±0.484 vs 1.425±0.359 g/L,P=0.239,fourth week: 1.193±0.375 vs 1.488±0.355 g/L,P=0.050).In the fifth week,the two groups of patients were still mechanically ventilated.The TRF level of the INT group was significantly higher than that of the SNT group(1.696±0.232 vs 1.281±0.337 g/L,P=0.007).4.Effect of INT on muscle mass and diaphragmatic atrophyThe BCh E of the two groups of critically ill patients receiving mechanical ventilation decreased to varying degrees.In the first and second weeks,the BCh E levels were similar in both groups(first week: 5863.67±1739.43 vs 5558.85 ±1495.83 IU/L,P=0.552,second week: 4944.29±1622.46 vs 4276.75±1191.95 IU/L,P=0.143),while from the third to fifth weeks,the BCh E levels of the patients in the INT group were significantly higher than those of the patients in the SNT group(third week: 3373.65±1247.95 vs 2550.19±1008.69 IU/L,P=0.046,fourth week: 3854.71±1107.25 vs 2639.42±999.79 IU/L,P=0.008,fifth week: 3676.00±1262.83 vs 2403.00±908.98 IU/L,P=0.035).Patients in the two groups had different degrees of diaphragm atrophy after mechanical ventilation.The percentage decreased in the second and third week(second week: 11.95±8.18 vs 11.4±8.15 %,P=0.830,third week: 16.18±9.86 vs 10.23±11.93 %,P=0.202)were not different.However,the Ddi% of the INT group was significantly less than that of the SNT group in the fourth week(7.14±9.62 vs 17.00±6.68 %,P=0.046).These improvements were more pronounced in the fifth week(5.33±14.15 vs 21.00±0.82 %,P=0.012).5.Effect of INT on clinical outcomesThere were 6 deaths in the SNT group,of which 1 patient failed to wean from mechanical ventilation.The other 15 patients of the SNT group were successfully weaned from mechanical ventilation and were transferred out of the ICU because of improved conditions.In the INT group,4 patients died and 17 patients were successfully weaned from mechanical ventilation.One of the 17 patients experienced aggravated illness after the successful weaning and died.The remaining 16 patients of the INT group improved and were transferred out of the ICU.There was no difference in the success rate of weaning(16/21 [76.19%] vs 17/20 [85.00%],P=0.477),mortality(6/21 [28.57%] vs 4/20 [20%],P=0.523)and tracheotomy rate(5/21 [23.81%] vs 10/20 [50.00%],P=0.080).INT between the two groups.In addition,no significant differences between the duration of MV(23.29±11.81 vs 22.59±9.99 d,P=0.876)and the duration of ICU hospitalization(28.40±11.78 vs 27.94±11.44 d,P=0.912)of ICU survivors were found between the two groups also.6.Effect of INT on respiratory mechanicsIn fourth and fifth weeks,the oxygenation index of the INT group was higher than that of the SNT group(fourth week: 393.86±59.30 vs 330.17±81.65 mm Hg,P=0.031,fifth week: 431.14±80.30 vs 301.50±65.27 mm Hg,P=0.023).No significant differences in Pa CO2,Vt,RSB,and Crs were found between the two groups during MV in the weekly comparison(P >0.05).ConclusionsApplication of additional protein supplements for ill critically mechanical ventilation patients,compared with standard nutrition treatment,there was no significant difference in BCh E,NB,PRE,TRF in intensive nutrition treatment in the first three weeks.It could not improve metabolic status and did not protect against acute diaphragm atrophy caused by diseases.However,after the third week,increasing protein as a nutrient substrate improved the anabolism and nutritional status of the patient.It also reduced diaphragm atrophy in the patients.This study has demonstrated that increasing protein intake to 2.0 g/kg/day does not lead to improved weaning from prolonged mechanical ventilation in ICU patients.