| 【Objective】Delirium is a common neuropsychiatric syndrome in the intensive care unit(ICU),leading to various degrees of near-or long-term adverse outcomes.The clinical manifestations of delirium in the ICU are complex and varied,and the severity of delirium can be influenced by the timing of the first attack,the duration,and the type.The causes of delirium also vary,including obvious external risk factors,as well as some individual physiological factors,such as the level of inflammatory changes due to metabolic abnormalities.The prevalence of delirium in critically ill children in the ICU ranges from12% to 47%,and there are no in-depth studies on the correlation between the heterogeneity of clinical phenotypes,inflammatory markers and the characteristics of delirium-attack in critically ill children in the ICU.Therefore,this study aims to comprehensively describe the characteristcis of delirium symptoms in critically ill children in ICU by the timing of the first attack,the duration,the type,etc.;and to predict the risk of delirium-attack by both clinical phenotypes and physiological mechanisms of high-risk factors,and to comprehensively understand the characteristics of delirium-attack.It aims to construct a more optimized symptom management plan to reduce its incidence and relieve symptoms,and ultimately improve the clinical efficacy of severely ill children.The specific objectives of the study include:1.To investigate the current status of symptoms of delirium-attack in critically ill children.2.To identify characteristics of high-risk clinical phenotypes in critically ill children.3.To analyze the inflammatory markers related to delirium-attck in critically ill children.4.To explore the predictive value of clinical phenotypic features combined with inflammatory markers for delirium in critically ill children.5.To construct a preliminary protocol for symptom management of delirium in critically ill children.【Methods】The study is divided into four parts:Part One.Study on the current status and high-risk clinical phenotypic characteristics of delirium-attack in critically ill children in ICU A cross-sectional study was conducted to recruit 634 children from a pediatric ICU of a tertiary hospital using convenience sampling method.Information on Demographics and disease was collected,and condition of delirium was evaluated at bedside.Onset of delirium,and characteristics of the timing of first attack,duration,types were described.Based on the "individual-centered" method,"hypoxia,sepsis,metabolic abnormalities,and sedation"---the four common high-risk factors for delirium-attack,were analyzed by the Latent Class Analysis(LCA)to identify the high-risk clinical phenotypic characteristics of delirium in critically ill children in the ICU,and to compare the characteristics of delirium corresponding to different clinical phenotypic characteristics difference.Part Two.Study on delirium-related inflammatory markers for critically ill childern in ICU1.Scoping Review: Based on the five-step method proposed by Arksey and O’Malley(identify research questions,determine relevant researches,search for literature,extract data,collect,summarize,and report).Search the database from January 2000 to December2017,select eligible literatures and summarize the included ones.2.Study on the relationship between inflammatory markers and delirium-attack in critically ill children An investigation was conducted to collect CRP,NLR,PLR,PWR levels and interleukin(IL＿6,IL＿8,IL＿10)levels during ICU stay.To analyze the levels of common inflammatory biomarkers in ICU,including CRP,NLR,PLR,and PWR during ICU stay.Delirium-related inflammatory biomarkers in critically ill children in the ICU were analyzed to compare the differences in inflammatory marker levels between groups,with the onset and severity of delirium as the dependent variable.Part Three.Predictive value of clinical phenotypic characteristics combined with inflammatory markers for delirium in critically ill children in the ICU Data of 634 critically ill children in the first part of the study were used to analyze high-risk factors using multi-factor logistic regression analysis based on demographic data,clinical disease data,inflammatory markers,clinical phenotypic features,delirium characteristics and some other variables.And then to explore the precise predictive value of clinical phenotypic features combined with inflammatory markers on delirium-attack.199 children in ICU having delirium-attack were included,and independent risk factors for persistent delirium-attack in critically ill children were identified by univariate analysis and multifactorial logistic regression analysis,and the predictive value of inflammatory markers and PRISM scores,etc.for persistent delirium-attack was explored.Part Four.Construction of a preliminary protocol for symptom management of delirium in critically ill children in ICU In this part,on the basis of summarizing the characteristics of high-risk clinical phenotypes and the association pattern of inflammatory markers of delirium in critically ill children in ICU,we clarify the intervention elements of the management plan of delirium based on the MRC Complex Intervention Framework,and combine literature research and qualitative interviews to make a preliminary symptom management plan of delirium in critically ill children in ICU,including intervention target,intervention time,intervention methods and contents,and forming a "stratified and graded" symptom management strategy.The "stratified,time-divided,and graded" symptom management strategy was developed.【Result】1.Results of the analysis of symptom characteristics of delirium-attack in critically ill children.A total of 634 critically ill children in ICU were included in this study,including 345males(54.40%),with a median ICU stay of 3.26 days;during treatment,a total of 138(21.8%)children were treated with mechanical ventilation,78(90.2%)were restrained,and 26% had PRISM scores at critical(7-11 points)or higher risk(>12 points).Delirium occurred in a total of 199(31.4%)children,and the longer staying in the ICU,the higher the incidence of delirium.The incidence of delirium was 67.4% in the mechanically ventilated group,33.4% in the restrained group,and 76.9% in the high-risk PRISM score group.Regarding the characteristics of delirium episodes in critically ill children,175(87.9%)children had their first delirium-attack in the first three days of ICU admission;in terms of the number of incidence,68.6% of children had 0 delirium days,10.9% had 1delirium day,and 4.3% had 6 delirium days or more。2.Results of characterization of high-risk clinical phenotypes of delirium episodes in critically ill children in the ICU.For the four main high-risk clinical phenotypes,27.3% of all participating children had abnormal renal function,of which the rate of children with delirium was 60.3%;16.7% of children with septic infection had delirium incidence of 47.2%;33.3% of children with hypoxia had delirium episodes of which the rate was 57.3%.The results of the chi-square test analysis showed that the four high-risk clinical phenotypes were significantly associated with the time to first attack,frequency,duration,and types of delirium in children(p < 0.001).3.Results of latent class analysis of high-risk clinical phenotypic features of delirium in critically ill children in the ICU.Results of the latent class analysis showed that clinical phenotypic characteristics were grouped into 3 categories(Entropy = 0.76): high sedation low sepsis category in group A(N = 189),high sepsis low sedation category in group B(N = 62),and low sedation mixed category in group C(N = 383),with significant differences in gender(p = 0.040),admission diagnosis(p < 0.001),admission mode(p < 0.001),mechanical ventilation(p <0.001)and restraint use(p = 0.027)were significantly different.4.Study on the prediction of delirium in critically ill children in ICU by different high-risk clinical phenotype types The results showed that there were significant differences between children with different high-risk clinical phenotype types in terms of whether delirium occurred,type of delirium,duration,time of the first attack,and days of ICU stay(p < 0.001).Group A had the highest incidence of delirium,while children in group B had more opportunity to have low-activity delirium and multiple attacks of delirium with high severity and potentially worse healing.5.Study on delirium-related inflammatory markers in critically ill children in the ICU3475 papers were retrieved in the scoping review,and 22 full-text papers were finally included,which were published from 2008 to 2017.The types of delirium-related inflammatory markers,study designs,and study subjects in the included literature were analyzed,and it was found that the current domestic and international studies on delirium-related inflammatory markers mainly focused on CRP,interleukins(IL-1β,IL-6,IL-8,IL-10,and IL-12),TNF-α,and NLR and PLR indicators.6.Analysis of inflammatory markers in critically ill children in the ICU with different clinical phenotypic characteristics It showed that the overall level of CRP during the ICU stay in this sample was(25.25±21.92)mg/L,with the highest overall CRP of(40.12±43.34)mg/L on the second day of ICU admission and(27.92±28.75)mg/L on the day of the first attack of delirium,with all three figures being 10 mg/L above the reference normal value.The NLR and PLR on the day of the first delirium episode were higher than the overall level during the ICU stay.CRP-F and NLR-M 、 PLR-M were significantly correlated with the severity of delirium.7.Precise management of clinical phenotype characteristics combined with inflammatory markers of delirium in critically ill children.(1)Multifactorial logistic regression analysis showed that subgroups of clinical phenotypic characteristics(OR:0.48;p<0.001),age(OR:0.97;p<0.001),PRISM score(OR:1.31;p<0.001),duration of infection(OR:1.21;p < 0.001),and CRP(OR:0.97;p=0.029)were independent risk factors for delirium in critically ill children in ICU.Further ROC analysis of CRP combined with clinical phenotypic features and days of infection duration showed that the AUC of the three indicators predicting delirium was0.772,0.795 and 0.760,respectively,and the AUC of CRP combined with clinical phenotypic features and days of infection duration as independent risk factors predicting delirium was 0.918(95% CI: 0.894-0.943),with a sensitivity and specificity of 82% and90%,respectively,at a cutoff value of 0.35.(2)Accurate predictive value of clinical phenotypic features combined with inflammatory markers for the severity of delirium in critically ill children.199 children with delirium in ICU were divided into two groups according to the severity of single episode or multiple episodes,and the variables of demographic data,clinical disease data,inflammatory markers and characteristics of delirium episodes were included.Independent risk factors for persistent delirium episodes were determined by univariate analysis and multifactorial logistic regression analysis,and CRP combined with IL＿6,NLR and PRISM scores were ROC curve analysis was performed.The results showed an AUC of 0.895(95% CI:0.802-0.989)for the joint prediction of persistent delirium episodes,with a sensitivity and specificity of 77% and 92%,respectively,at a cut-off value of 0.75.8.Study on the construction of a management plan for delirium in critically ill children in ICUBased on the MRC Complex Intervention Framework,we clarified the intervention elements of the precise management plan for delirium in critically ill children,and constructed a precise management plan for delirium in critically ill children in the ICU,forming a "stratified,time-divided,and graded" precise management in terms of intervention targets,intervention time,intervention methods and contents.【Conclusion】1.Heterogeneity exits in the high-risk clinical phenotypic features for the occurrence of delirium in ICU critically ill children,and children with these different features have different incidence of delirium,suggesting that different clinical phenotypes should be precisely identified to improve the accuracy of predicting delirium.2.Specific inflammatory markers existed in critically ill children in ICU(CRP-F and NLR-M),among which,CRP combined with clinical phenotypic features has a better predictive value for delirium.3.Based on clinical phenotype classification,inflammatory factor analysis,and the combined use of both,the predictive accuracy of delirium was improved.4.Based on the Complex Intervention Framework,we initially constructed a management plan for delirium in critically ill children in ICU,focusing on the intervention target population,intervention time,intervention methods and contents,and the "stratified,time-divided,and graded" management plan is of practical guidance for ICU nurses on delirium management. |
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