| Background Critical illness adults in intensive care unit(ICU)are usually associated with stress reaction,gastrointestinal motility dysfunction and intestinal dysbacteriosis before admission and during hospitalization,resulting in a strikingly high prevalence of malnutrition(ranging from 38% to 78%).Enteral nutrition(EN)support therapy has been recommended as the preferred nutrition support therapy method.The main benefit of enteral nutrition comes from mitigation of the development of a protein-calorie deficit,maintenance of structural and functional gut integrity,a decrease in intestinal permeability,and attenuation of the inflammatory response.However,health professionals still have difficulties in providing early EN support and in achieving and/or maintaining nutrition goals.Caloric intake less than the goal reflects underfeeding.The prevalence of underfeeding is above 50%.Underfeeding is closely related to adverse clinical outcomes.The major problems remaining to be solved include that the definition of underfeeding is still lack of unanimity,the risk factors for underfeeding and the clinical efficacy of prevention measures against underfeeding remains unclear.Objective 1.To systematically review and meta-analyze on the breadth of definitions used,the prevalence of underfeeding,the risk factors for underfeeding,and the relationship between underfeeding and outcome in critically ill adults in ICU,in order to supply the baseline data for identifying the key points of the problems and confirm the importance of preventing and reducing underfeeding for critically ill adults in ICU.2.To investigate and analyze the key period of underfeeding occurrence and development to enrich the data of critically ill adults in China and supply baseline data for constructing an individualized underfeeding prevention program for critically ill adults in ICU through a crosssectional study and a questionnaire.3.To systematically review the guidelines and expert consensuses on underfeeding preventive measures for critically ill adults in ICU,forming a toolbox to prevent underfeeding by evaluating the evidence intensity and consistency.Then,expert consultation is combined to construct an individualized underfeeding prevention program for critically ill adults in ICU in the sampling hospitals.4.To evaluate the efficacy and feasibility of the preventive program for underfeeding in critically ill adults to provide evidence for clinical evidence-based decision-making on preventing and reducing underfeeding for critically ill adults in ICU.Materials and Methods 1.Definition,prevalence,risk factors and outcome of underfeeding among critically ill adults receiving enteral nutrition in ICU: a systematic review and meta-analysis This study systematically searched the Medline,EMBASE and Cochrane Library databases from the inception date to July 7,2020.We also used a manual search strategy to retrieve relevant articles referenced by the retrieved publications.Trials were selected based on the population included critically ill adult patients admitted to intensive care unit(ICU)who received EN and were aged ≥18 years old,and the outcomes included underfeeding.The risk of bias of the included Randomized Controlled Trial(RCT)was based on the Cochrane 5.1.0 risk-of-bias criteria,cohort and case-control studies were assessed with the Newcastle-Ottawa Scale(NOS),and cross-sectional studies were evaluated using the risk of bias assessment tool recommended by the Agency for Healthcare Research and Quality(AHRQ),the methodological quality of nonrandomized intervention studies was completed using the Methodological Index for Nonrandomized Studies(MINORS)criteria.The data were qualitatively described and quantitatively analyzed by meta-analysis and meta regression analysis to explore the cutoff point for underfeeding and to estimate the prevalence,risk factors and important patient-centered outcomes of underfeeding.2.A multicenter survey on underfeeding and barriers to enteral feeding among critically ill adults in ICU 2.1 A multicenter survey on underfeeding during enteral nutrition among critically ill adults in ICU Three Third Grade Class A General Hospitals in Chengdu served as sample hospitals,critically ill adults were selected for analysis from April to July 2020.The included ICU patients based on the population received EN in the first week after admission to ICU and were aged ≥18 years old.The main survey included the individual basic information,disease severity and nutrition status,the application of nutritional support during the first week after admission to ICU,the prevalence of total duration of underfeeding(failed to receive at least 60% of energy targets)and iatrogenic underfeeding(occurred primarily due to human factors),and the clinical outcomes during hospitalization in critically ill adults receiving enteral nutrition.Logistic regression and Cox regression were used to analyze the risk factors and clinical outcomes of underfeeding in critically ill adults receiving enteral nutrition.2.2 Barriers to delivery of enteral nutrition for adult ICU patients in medical staff Medical staff selected from the sample hospitals were investigated using the Chinese version of the “Barriers to enteral feeding critically ill patients questionnaire”,the translated questionnaire developed by Cahill’s team,revised by Huang Jingying and his colleagues.3.Construction of a preventive program for underfeeding during enteral nutrition in adult ICU patients 3.1 Guidelines and expert consensuses concerning underfeeding prevention in adult ICU patients: a systematic review This study systematically searched the Medline,EMBASE,Cochrane Library,CNKI,VIP and Wan Fang databases,as well as the websites of global guidelines,nutrition association and critical care medicine associations to collect underfeeding prevention guidelines and expert consensuses in critically ill adults from inception to June 8,2020.The methodological quality of the guidelines and expert consensuses were evaluated using the Appraisal of Guidelines for Research and Evaluation II(AGREE II).The evidence intensity and consistency of preventive measures for underfeeding in adult critically ill patients were also evaluated using the evaluation standard developed by Alper’s team.3.2 Construction of a preventive program for underfeeding during enteral nutrition among critically ill adults in ICU based on the expert consultation method Delphi expert consultation and multicriteria decision analysis(MCDA)expert consultation were adopted to evaluate the importance and clinical practicability of preventive measures for underfeeding in adult critically ill patients and finally form an individualized preventive program of underfeeding for critically ill adults.4.Empirical study on the application of a preventive program of underfeeding during enteral nutrition among critically ill adults in ICU Parallel nonrandomized clinical trial with an additional historical control group was conducted from April to December 2020 in three sample hospitals.The divided four experimental groups were divided as follows: the preintervention,postintervention,precontrol and postcontrol groups.The classic model of behavior change,the “knowledge,attitude,belief,practice” model,was used as theoretical guidance.We applied a preventive program of underfeeding in critically ill adults in the intervention group,no preventions were given to the control group.Multivariate logistic regression,multivariate Cox regression and a difference-indifference(DID)model were used to analyze whether applying a preventive strategy of underfeeding in critically ill adults was able to increase the adequacy of enteral nutrition delivery,prevent and reduce underfeeding,and improve clinical outcomes in critically ill patients.Results 1.Definition,prevalence,risk factors and outcome of underfeeding among critically ill adults receiving enteral nutrition in ICU: a systematic review and meta-analysis A total of 12,129 reports were identified,and ninety-two trials(122 reports)met the inclusion criteria,including twenty-four RCTs,six quasi-experimental studies,twenty-seven cohort studies and thirty-five cross-sectional studies.A total of 56,426 patients were included in the systematic review and quantitative synthesis.Among these,the average age of the included critically ill adults was 60 years.Of the total patients,88.5% was mixed ICU patients.Sixty-six trials(69 reports)provided definitions for underfeeding,forty-eight studies(72.7%,48/66)defined underfeeding as an inadequate amount of nutrients delivered as a proportion of the “energy requirements” with values of 25 to 100% chosen as the threshold.The time from the commencement of feeding to the diagnosis of underfeeding was defined in 24 studies.In 18 of the 24 studies,the provision of an inadequate amount of nutrients delivered in the first 3-7 days was used to define underfeeding in the acute phase.Twenty-five studies reported the prevalence of underfeeding,the pooled prevalence of underfeeding was 49.5%(range 38.8 to 60.1%)by meta-analysis.Quantitative analysis of risk factors for underfeeding was extracted from 7 studies.Underprescription,the presence of pelvic/lumbar spine trauma,problems with feeding tubes,airway management,abdominal surgery or trauma,receiving contrast via a tube to prepare for a computed tomography scan,and gastrointestinal intolerance were the main risk factors for underfeeding,in addition,extended length of stay in ICU,implementation of enteral nutrition feeding protocol,and the enteral nutrition pathway with a double lumen tube were the main protective factors for underfeeding.Compared to adequately fed critically ill adults,underfed critically ill adults during hospitalization had an increased risk of short-term all-cause mortality,including 28-day all-cause mortality,ICU mortality and hospital mortality [OR=1.12,95% CI:1.00 to 1.25,low certainty].Underfed critically ill adults in acute phase had an increased risk of short-term all-cause mortality [OR=1.42,95% CI:1.00 to 2.01,low certainty] and a shorter hospital length of stay [MD=-3.80 days,95% CI:-6.14 to-1.46,very low certainty].Underfeeding in acute phase did not affect infection outcomes [OR=0.97,95% CI: 0.61 to 1.53,low certainty] or ICU length of stay [MD=0.39 days,95% CI:-2.02 to 2.80,very low certainty].2.A multicenter survey on underfeeding and barriers to enteral feeding among critically ill adults in ICU 2.1 A multicenter survey on underfeeding during enteral nutrition among critically ill adults in ICU In 809 patients treated in the mixed ICU of these three sample hospitals,295 patients(36.5%)met the inclusion criteria.The mean age was(68.0±16.7)years old.On the third day after the initiation of enteral nutrition,there were 156 cases with underfeeding in critically ill adults receiving enteral nutrition(54.2%,156/288)and 72 cases with iatrogenic feeding in the total duration of underfeeding(46.2%,72/156).Additionally,there were 84 cases with underfeeding in critically ill adults receiving enteral nutrition(36.1%,84/233)and 35 cases with iatrogenic feeding in the total duration of underfeeding(41.7%,35/84)on the seventh day.The results of multivariate logistic regression analysis showed that the risk factors for the total duration of underfeeding on the third day included an increased level of acute gastrointestinal injury(AGI)[OR=4.02,95% CI: 1.43 to 11.31],increased target energy requirement [OR=1.20,95% CI: 1.05 to 1.38],and advanced the time of initiation of enteral nutrition [OR=4.80,95% CI: 1.06 to 21.66].In addition,the risk factors of the total duration of underfeeding on the seventh day includes the following: the high scores of m NUTRIC [OR=22.81,95% CI: 2.61 to 199.56],an increased AGI level [OR=8.92,95% CI: 1.43 to 11.31],abdominal surgery or trauma [OR=10.56,95% CI: 1.47 to 75.58],increased target energy requirement [OR=1.32,95% CI: 1.16 to 1.50],and advanced the time of initiation of enteral nutrition [OR=8.57,95% CI: 1.60 to 245.89] and enteral nutrition was suspended for more than one day within 7 days [OR=3.46,95% CI: 1.25 to 9.61].The risk factors for the iatrogenic underfeeding on the third day included critically ill adults with surgical diseases [OR=9.76,95% CI: 2.55 to 37.32] and delayed enteral nutrition initiation time [OR=11.89,95% CI: 1.84 to 76.74].The risk factors for the iatrogenic underfeeding on the seventh day included suspension of enteral nutrition for more than one day within 7 days [OR=5.08,95% CI: 1.25 to 20.63].The results of the reference table embodying the relation between the risk score and the risk probability of iatrogenic underfeeding showed that the risk score of iatrogenic underfeeding in critically ill adults was over 2 scores,the probability of the existence or occurrence of iatrogenic underfeeding on the third day or the seventh day was more than 90%.By excluding inpatients discharged from the ICU without discharge criteria,the results of multivariate Cox regression analysis showed that the risk of hospitalization death was increased in the underfed critically ill adults on the third day [HR=5.20,95% CI: 1.21 to 22.34].However,there was no significant difference in the risk of ICU death between underfed and adequately fed critically ill adults on the third day [HR=3.37,95% CI: 0.61 to 18.58].There was no significant difference in the risk of hospitalization death and ICU death between underfed and adequately fed critically ill adults on the seventh day [HR=0.40,95% CI: 0.11 to 1.38;HR=0.34,95% CI: 0.08 to 1.37].2.2 Barriers to delivery of enteral nutrition for adult ICU patients in medical staff A total of 141 medical staff were enrolled in the survey.We obtained 126 valid questionnaires(89.4% efficiency).The basic information of the medical staff who completed the valid questionnaire was as follows.In total,40 medical staff(31.7%)majored in critical care medicine,78 medical staff(61.9%)majored in nursing,8 medical staff(6.4%)majored in other clinical specialties.Sixty-eight medical staff(54.0%)had less than five years of related work experience,44 medical staff(34.9%)had 6-10 years of related work experience,8 medical staff(6.3%)had 11-15 years of related work experience,6 medical staff(4.8%)had 16-20 years of related work experience.The average scores of the 3 subscales of the Chinese version of the barriers to enteral feeding critically ill patients questionnaire were "behavior and attitude of ICU medical staff"(3.3 scores),"enteral nutrition supply"(3.1 scores)and "ICU resources"(2.0 scores).3.Construction of a preventive program for underfeeding during enteral nutrition in adult ICU patients 3.1 Guidelines and expert consensuses concerning underfeeding prevention in adult ICU patients: a systematic review A total of 5997 reports were identified,and 6 guidelines and 3 expert consensuses related to underfeeding prevention in critically ill adults were included.According to AGREE Ⅱ,one was A-level,and seven were B-level,and one was C-level.There were 19 related recommendations mainly involving underfeeding prevention for critically ill adults.The recommendations on preventive measures/strategies for underfeeding in critically ill adults mainly include two aspects: standardizing the enteral nutrition feeding process and monitoring and promoting feeding during enteral nutrition feeding.There is a strong body of evidence from systematic reviews and RCTs in supporting the use of standardizing the enteral nutrition feeding process in preventing underfeeding in critically ill adults.There are no high-quality clinical evidences comparing the effect of a certain type or frequency of monitoring on clinical outcome in critically ill adults.3.2 Construction of a preventive program for underfeeding during enteral nutrition among critically ill adults in ICU based on the expert consultation method Expert consultation was achieved in two stages using the Delphi expert consultation method and multicriteria decision analysis.In the first stage of Delphi expert consultation,two rounds of expert consultation were performed.The expert efficiency coefficients were 88%(22/25)and 100%(22/22),respectively.The expert authority coefficients were 0.85 and 0.91,respectively.Kendall’s W was 0.076(P=0.018)in the second round of the Delphi expert consultation.In the second stage of multicriteria decision analysis,one round of expert consultation was performed,and the expert efficiency coefficient was 85%(17/20).The expert authority coefficients were 0.94,and Kendall’s W was 0.351(P<0.001).Through two rounds of Delphi expert consultation,a preliminary preventive strategy of underfeeding in critically ill adults consisting of 3 subscales was established,including rules and procedures;medical staff’s knowledge,attitude,belief,practice;and ICU resources.Finally,in the second stage of multicriteria decision analysis,national experts suggested that 6 strategies should be bundled as the key steps of the enteral nutrition feeding process for preventing underfeeding in critically ill adults.The six nutrition bundle strategies included nutrition screening;disease-based nutrition supply(energy and protein)goals,assessment and adjustment at different stages;the time of initiation of enteral nutrition;enteral nutrition supply pathway;monitoring indicators during enteral nutrition;and criteria of enteral nutrition feeding intolerance and intervention methods.4.Empirical study on the application of a preventive program of underfeeding during enteral nutrition among critically ill adults in ICU In 1554 patients treated in the mixed ICU of these three sample hospitals,609 patients(39.2%)met the inclusion criteria.There were 101,194,120 and 194 critically ill adults in the preintervention,precontrol,postintervention and postcontrol groups,respectively.The results of multivariate logistic regression analysis showed that the before and after changes in the risk of the total duration of underfeeding on the third day,the total duration of underfeeding on the seventh day,and iatrogenic underfeeding on the third day in the intervention groups were reduced by 65% [OR=0.35,95% CI: 0.15 to 0.81],83% [OR=0.17,95% CI: 0.05 to 0.58] and 77% [OR=0.23,95% CI: 0.08 to 0.67],respectively.However,the before and after changes in the risk of iatrogenic underfeeding on the seventh day in the intervention groups did not reach statistical significance [OR=0.28,95% CI: 0.06 to 1.32].Compared with the parallel,nonrandomized control groups,the before and after changes in the risk of the total duration of underfeeding on the third day and seventh day in the control groups were reduced by 57% [OR=0.43,95% CI: 0.26 to 0.73] and 52% [OR=0.48,95% CI: 0.24 to 0.95],respectively.However,the before and after changes in the risk of the iatrogenic underfeeding on the third and seventh day in the control groups did not reach statistical significance [OR=1.01,95% CI: 0.99 to 1.02;OR=0.59,95% CI: 0.27 to 1.27].The net effect of implementing the preventive strategy of underfeeding in critically ill adults was to increase the proportion of enteral nutrition feeding adequacy by 11.4%(t=2.08,P=0.038)on the third day and 13.9%(t=2.23,P=0.026)on the seventh day after controlling for the factors related to underfeeding by the DID model.The results of multivariate Cox regression analysis showed that the before and after changes in the risk of hospitalization death and ICU death were the same in the intervention groups [HR=0.61,95% CI:0.30 to 1.24;HR=0.75,95% CI:0.40 to 1.39] and in the control groups[HR=0.82,95% CI:0.53 to 1.26;HR=0.74,95% CI:0.50 to 1.12].Conclusion 1.Underfeeding is usually defined as intakes below a certain threshold of the percentage of energy requirements.However,values of 60% chosen as cut-off value in acute phase may be appropriate.The prevalence of underfeeding may be higher in acute phase among critically ill adults.Underfeeding in acute phase among critically ill adults is the key points of intervention.2.Underfeeding occurred primarily due to human factors in the sample hospitals.Iatrogenic underfeeding is critical for prompt recognition and the key points of intervention.Medical staff’s knowledge,attitude,belief,practice is the main barrier factor in achieving or maintaining enteral nutrition goals for critically ill adults in the sample hospitals.3.Enteral feeding protocols should be designed and implemented to prevent and reduce underfeeding among critically ill adults in ICU.We recommend that a nutrition bundle including six strategies should be implemented as the key steps of the enteral nutrition feeding process to prevent underfeeding in critically ill adults.The six nutrition bundle strategies were nutrition screening;disease-based nutrition supply(energy and protein)goals,assessment and adjustment at different stages;the time of initiation of enteral nutrition;enteral nutrition supply pathway;monitoring indicators during enteral nutrition;and criteria of enteral nutrition feeding intolerance and intervention methods.4.Application of the preventive program of underfeeding among critically ill adults in ICU was able to prevent and reduce the total duration of underfeeding on the third and seventh days and iatrogenic underfeeding on the third day,further research need to expand the sample size to confirm the clinical effectiveness of the preventive strategy in reducing iatrogenic underfeeding on the seventh day as well as the risks of hospitalization death and ICU death. |
