Deciphering the iron enigma: Navigating the complexities of iron metabolism in critical illness

Iron is a double-edged sword!Despite being essential for numerous physiological processes of the body,a dysregulated iron metabolism can result in tissue da-mage,exaggerated inflammatory response,and increased susceptibility to infection with certain pathogens that thrive in iron-rich environment.During sepsis,there is an alteration of iron metabolism,leading to increased transport and uptake into cells.This increase in labile iron may cause oxidative damage and cellular injury(ferroptosis)which progresses as the disease worsens.Critically ill patients are often complicated with systemic inflammation which may contribute to multiple organ dysfunction syndrome or sepsis,a common cause of mortality in intensive care unit.Originally,ferritin was known to play an important role in the hematopoietic system for its iron storage capacity.Recently,its role has emerged as a predictor of poor prognosis in chronic inflammation and critical illnesses.Apart from predicting the disease outcome,serum ferritin can poten-tially reflect disease activity as well.

Mental health status among COVID-19 patients survivors of critical illness in Saudi Arabia:A 6-month follow-up questionnaire study

BACKGROUND Psychological assessment after intensive care unit(ICU)discharge is increasingly used to assess patients'cognitive and psychological well-being.However,few studies have examined those who recovered from coronavirus disease 2019(COVID-19).There is a paucity of data from the Middle East assessing the post-ICU discharge mental health status of patients who had COVID-19.AIM To evaluate anxiety and depression among patients who had severe COVID-19.METHODS This is a prospective single-center follow-up questionnaire-based study of adults who were admitted to the ICU or under ICU consultation for>24 h for COVID-19.Eligible patients were contacted via telephone.The patient’s anxiety and depression six months after ICU discharge were assessed using the Hospital Anxiety and Depression Scale(HADS).The primary outcome was the mean HADS score.The secondary outcomes were risk factors of anxiety and/or depression.RESULTS Patients who were admitted to the ICU because of COVID-19 were screened(n=518).Of these,48 completed the questionnaires.The mean age was 56.3±17.2 years.Thirty patients(62.5%)were male.The main comorbidities were endocrine(n=24,50%)and cardiovascular(n=21,43.8%)diseases.The mean overall HADS score for anxiety and depression at 6 months post-ICU discharge was 11.4(SD±8.5).A HADS score of>7 for anxiety and depression was detected in 15 patients(30%)and 18 patients(36%),respectively.Results from the multivariable ordered logistic regression demonstrated that vasopressor use was associated with the development of anxiety and depression[odds ratio(OR)39.06,95% confidence interval:1.309-1165.8;P<0.05].CONCLUSION Six months after ICU discharge,30% of patients who had COVID-19 demonstrated a HADS score that confirmed anxiety and depression.To compare the psychological status of patients following an ICU admission(with vs without COVID-19),further studies are warranted.

Sleep during and following critical illness:A narrative review

Sleep is a complex process influenced by biological and environmental factors.Disturbances of sleep quantity and quality occur frequently in the critically ill and remain prevalent in survivors for at least 12 mo.Sleep disturbances are associated with adverse outcomes across multiple organ systems but are most strongly linked to delirium and cognitive impairment.This review will outline the predisposing and precipitating factors for sleep disturbance,categorised into patient,environmental and treatment-related factors.The objective and subjective methodologies used to quantify sleep during critical illness will be reviewed.While polysomnography remains the gold-standard,its use in the critical care setting still presents many barriers.Other methodologies are needed to better understand the pathophysiology,epidemiology and treatment of sleep disturbance in this population.Subjective outcome measures,including the Richards-Campbell Sleep Questionnaire,are still required for trials involving a greater number of patients and provide valuable insight into patients’experiences of disturbed sleep.Finally,sleep optimisation strategies are reviewed,including intervention bundles,ambient noise and light reduction,quiet time,and the use of ear plugs and eye masks.While drugs to improve sleep are frequently prescribed to patients in the ICU,evidence supporting their effectiveness is lacking.

Predictive value of controlling nutritional status score for progression to chronic critical illness in elderly patients with sepsis

Objective:To investigate the predictive value of controlling nutritional status(CONUT)score for progression to chronic critical illness sepsis in elderly patients,and to construct a predictive model based on CONUT score histogram.Methods:739 elderly patients with sepsis admitted from January 2020 to December 2022 were selected as the study objects,and were divided into chronic critical illness group(n=188)and non-chronic critical illness group(n=551)according to whether chronic critical illness disease occurred.Clinical data of the patients were collected and compared.The predictive value of CONUT score,PNI and NLR in the progression of senile sepsis to chronic severe disease was compared,and the optimal threshold value was determined,which was used to convert the numerical variables into binary variables.Through univariate analysis and multivariate Logistic regression analysis,the risk factors affecting the progression of elderly sepsis patients to chronic critical illness disease were screened out,and the prediction model was built based on the nomogram.The efficacy and clinical utility of the prediction model were evaluated by the area under the ROC curve(AUC),calibration curve and decision curve analysis(DCA).Results:The best cut-off value for CONUT score in predicting elderly sepsis progressing to chronic critical illness was 4 points.The predictive performance of CONUT score(AUC=0.739)was better than that of PNI(AUC=0.609)and NLR(AUC=0.582)in elderly sepsis progressing to chronic critical illness(CONUT score vs PNI:Z=5.960,P<0.001;CONUT score vs NLR:Z=6.119,P<0.001).Univariate analysis showed that age,CCI score,SOFA score,sepsis shock,serum Lac,CONUT score,mechanical ventilation(MV),and continuous renal replacement therapy(CRRT)treatment were related to elderly sepsis progressing to chronic critical illness(P<0.05).Multivariate logistic regression analysis showed that CONUT score≥4 points,age≥75 years,CCI score≥3 points,SOFA score>5 points,sepsis shock,and serum Lac≥4 mmol/L were independent risk factors for elderly sepsis progressing to chronic critical illness(P<0.05).The nomogram showed that CONUT score had the greatest contribution value in predicting elderly sepsis progressing to chronic critical illness.Based on this,the nomogram prediction model had an AUC of 0.846[95%CI(0.812~0.879)],with a sensitivity of 75.5%and specificity of 81.3%,indicating good predictive performance.The calibration curve was close to the ideal curve,and the DCA threshold had clinical utility advantages when ranging from 0.1 to 0.9.Conclusion:The nomographic prediction model based on CONUT score can effectively predict the risk probability of senile sepsis progressing to chronic critical illness,helpful for clinicians to identify the high risk group of chronic and severe senile sepsis,which is helpful for clinicians to identify high-risk populations of elderly sepsis with chronic critical illness.

Critical illness polyneuropathy and myopathy:a systematic review

Critical illness polyneuropathy and critical illness myopathy are frequent complications of severe illness that involve sensorimotor axons and skeletal muscles, respectively. Clinically, they manifest as limb and respiratory muscle weakness. Critical illness polyneuropathy/myopathy in isolation or combination increases intensive care unit morbidity via the inability or difficulty in weaning these patients off mechanical ventilation. Many patients continue to suffer from decreased exercise capacity and compromised quality of life for months to years after the acute event. Substantial progress has been made lately in the understanding of the pathophysiology of critical illness polyneuropathy and myopathy. Clinical and ancillary test results should be carefully interpreted to differentiate critical illness polyneuropathy/myopathy from similar weaknesses in this patient population. The present review is aimed at providing the latest knowledge concerning the pathophysiology of critical illness polyneuropathy/myopathy along with relevant clinical, diagnostic, differentiating, and treatment information for this debilitat- ing neurological disease.

Artificial intelligence and computer simulation models in critical illness

Widespread implementation of electronic health records has led to the increased use of artificial intelligence(AI)and computer modeling in clinical medicine.The early recognition and treatment of critical illness are central to good outcomes but are made difficult by,among other things,the complexity of the environment and the often non-specific nature of the clinical presentation.Increasingly,AI applications are being proposed as decision supports for busy or distracted clinicians,to address this challenge.Data driven“associative”AI models are built from retrospective data registries with missing data and imprecise timing.Associative AI models lack transparency,often ignore causal mechanisms,and,while potentially useful in improved prognostication,have thus far had limited clinical applicability.To be clinically useful,AI tools need to provide bedside clinicians with actionable knowledge.Explicitly addressing causal mechanisms not only increases validity and replicability of the model,but also adds transparency and helps gain trust from the bedside clinicians for real world use of AI models in teaching and patient care.

Glucocorticoid and mineralocorticoid receptor expression in critical illness:A narrative review

The glucocorticoid receptor(GCR)and the mineralocorticoid receptor(MR)are members of the steroid receptor superfamily of hormone-dependent transcription factors.The receptors are structurally and functionally related.They are localized in the cytosol and translocate into the nucleus after ligand binding.GCRs and MRs can be co-expressed within the same cell,and it is believed that the balance in GCR and MR expression is crucial for homeostasis and plays a key role in normal adaptation.In critical illness,the hypothalamic-pituitary-adrenal axis is activated,and as a consequence,serum cortisol concentrations are high.However,a number of patients exhibit relatively low cortisol levels for the degree of illness severity.Glucocorticoid(GC)actions are facilitated by GCR,whose dysfunction leads to GC tissue resistance.The MR is unique in this family in that it binds to both aldosterone and cortisol.Endogenous GCs play a critical role in controlling inflammatory responses in critical illness.Intracellular GC concentrations can differ greatly from blood levels due to the action of the two 11β-hydroxysteroid dehydrogenase isozymes,type 1 and type 2.11β-hydroxysteroid dehydrogenases interconvert endogenous active cortisol and intrinsically inert cortisone.The degree of expression of the two isozymes has the potential to dramatically influence local GC availability within cells and tissues.In this review,we will explore the clinical studies that aimed to elucidate the role of MR and GCR expression in the inflammatory response seen in critical illness.

Characteristics of postintensive care syndrome in survivors of pediatric critical illness: A systematic review

AIM To synthesize the available evidence focusing on morbidities in pediatric survivors of critical illness that fall within the defined construct of postintensive care syndrome(PICS) in adults, including physical, neurocognitive and psychological morbidities.METHODS A comprehensive search was conducted in MEDLINE, EMBASE, the Cochrane Library, Psyc INFO, and CINAHL using controlled vocabulary and key word terms to identify studies reporting characteristics of PICS in pediatric intensive care unit(PICU) patients. Two reviewers independently screened all titles and abstracts and performed data extraction. From the 3176 articles identified in the search, 252 abstracts were identified for full text review and nineteen were identified for inclusion in the review. All studies reporting characteristics of PICS in PICU patients were included in the final synthesis. RESULTS Nineteen studies meeting inclusion criteria published between 1995 and 2016 were identified and categorized into studies reporting morbidities in each of three categories-physical, neurocognitive and psychological. The majority of included articles reported prospective cohort studies, and there was significant variability in the outcome measures utilized. A synthesis of the studies indicate that morbidities encompassing PICS are well-described in children who have survived critical illness, often resolving over time. Risk factors for development of these morbidities include younger age, lower socioeconomic status, increased number of invasive procedures or interventions, type of illness, and increased benzodiazepine andnarcotic administration.CONCLUSION PICS-related morbidities impact a significant proportion of children discharged from PICUs. In order to further define PICS in children, more research is needed using standardized tools to better understand the scope and natural history of morbidities after hospital discharge. Improving our understanding of physical, neurocognitive, and psychological morbidities after critical illness in the pediatric population is imperative for designing interventions to improve long-term outcomes in PICU patients.

Alcoholism and critical illness: A review

Alcohol is the most commonly used and abused drug in the world, and alcohol use disorders pose a tremendousburden to healthcare systems around the world. The lifetime prevalence of alcohol abuse in the United States is estimated to be around 18%, and the economic consequences of these disorders are staggering. Studies on hospitalized patients demonstrate that about one in four patients admitted to critical care units will have alcohol-related issues, and unhealthy alcohol consumption is responsible for numerous clinical problems encountered in intensive care unit(ICU) settings. Patients with alcohol use disorders are not only predisposed to developing withdrawal syndromes and other conditions that often require intensive care, they also experience a considerably higher rate of complications, longer ICU and hospital length of stay, greater resource utilization, and significantly increased mortality compared to similar critically ill patients who do not abuse alcohol. Specific disorders seen in the critical care setting that are impacted by alcohol abuse include delirium, pneumonia, acute respiratory distress syndrome, sepsis, gastrointestinal hemorrhage, trauma, and burn injuries. Despite the substantial burden of alcoholinduced disease in these settings, critical care providers often fail to identify individuals with alcohol use disorders, which can have significant implications for this vulnerable population and delay important clinical interventions.

Being in limbo: The experience of critical illness in intensive care and beyond

Critical illness is a sudden traumatising lived experience that affects the sufferer and their family throwing them into a crisis situation [1,2]. It is disruptive and alienating. Critically ill patients emerging from unconsciousness often suffer from confusion that could be momentary or lasting. There is an increasing number of critical illness survivors in intensive care units (ICU)1 with numerous life changing ongoing physiological and psychological sequelae from critical illness and ICU hospitalization, with inadequate ongoing treatment for ICU survivors. Medicalised accounts of critical illness fail to recognise the significant impact on the person, their embodied sense of self and their ability to move on with their life after they leave hospital. The main purpose of this study was to explore the experience of critically ill patients in ICU and beyond. This phenomenological study describes what it was like for twelve people to experience critical illness in ICU and in the months after discharge. The finding was that critical illness is an acute life threatening event with long lasting effects which translate into temporal and biographical disruption, imprisonment by the ICU and its therapies and being trapped in an alien body that is plagued by uncertainty and long lasting conditions arising from the critical illness and the ICU therapies. Critical illness survivors are left in a state of limbo characterised by a struggle to reclaim their precritical illness ICU identity and uncertainty about their future. Hence an overarching theme of being in limbo under which three major themes of 1) disrupttion, 2) imprisonment and 3) being trapped were generated from the study.

Study on the Accuracy of Serum Prealbumin Level in Predicting the Prognosis of Patients with Critical Respiratory Illness

Objective: To analyze the accuracy of serum prealbumin levels in predicting the prognosis of patients with critical respiratory illness. Methods: Fifty patients with critical respiratory illness admitted to our hospital from October 2022 to September 2023 were selected and divided into an observation group and a control group after condition assessment, with 25 cases in each group. The results of cholinesterase (ChE), prealbumin (PALB), albumin (ALB), aspartate aminotransferase (AST), total protein (TP), and forced expiratory volume (FEV1)/Predicted (Pred) of the two groups were measured. Results: The ChE levels of the observation group were lower than those of the control group, while the PALB and ALB levels of the observation group were higher than those of the control group (P < 0.05). The AST, TP, and FEV1 /Pred levels of the observation group were higher than those in the control group (P < 0.05). Conclusion: Serum PALB levels can be used as the main indicator for prognosis in critically ill respiratory patients.

Advancing critical care recovery:The pivotal role of machine learning in early detection of intensive care unit-acquired weakness

This editorial explores the significant challenge of intensive care unit-acquiredweakness(ICU-AW),a prevalent condition affecting critically ill patients,characterizedby profound muscle weakness and complicating patient recovery.Highlightingthe paradox of modern medical advances,it emphasizes the urgent needfor early identification and intervention to mitigate ICU-AW's impact.Innovatively,the study by Wang et al is showcased for employing a multilayer perceptronneural network model,achieving high accuracy in predicting ICU-AWrisk.This advancement underscores the potential of neural network models inenhancing patient care but also calls for continued research to address limitationsand improve model applicability.The editorial advocates for the developmentand validation of sophisticated predictive tools,aiming for personalized carestrategies to reduce ICU-AW incidence and severity,ultimately improving patientoutcomes in critical care settings.

Facilitating and hindering factors of community nurses'emergency and critical care treatment abilities:A qualitative study

BACKGROUND This study adopts a descriptive phenomenological approach to investigate the facilitators and barriers of community nurses'abilities in managing critical and emergency conditions.With the transition of healthcare systems to the community,the evolution of nursing practices,and the attention from policies and practices,community nurses play a crucial role in the management of critical and emergency conditions.However,there is still a lack of comprehensive understanding regarding the factors that promote or hinder their capabilities in this area.AIM To understand the facilitators and barriers of community nurses in managing critical and emergency conditions,exploring the fundamental reasons and driving forces influencing their treatment capabilities.METHODS This study utilized the destination sampling method between May 2023 and July 2023.It employed a descriptive phenomenological approach within qualitative research methodologies.Through objective sampling,17 community nurses from 7 communities in Changning District,Shanghai,were selected as the study subjects.Semi-structured interviews were conducted to gather data,which were subsequently organized and analyzed using Colaizzi's seven-step analysis method,leading to the extraction of final themes.RESULTS The barrier factors identified from the interviews encompassed three topics:resource allocation,professional factors,and personal literacy.The facilitators comprised three themes:professionalism,management attention,and training and continuing education.We identified that the root causes of the barriers included the lack of practical treatment experience among community nurses,insufficient awareness of self-directed learning,and limited knowledge and technical proficiency.The professional quality of community nurses and management attention serve as motivation for them to enhance their treatment abilities.CONCLUSION To enhance the capability of community nurses in treating acute and critical patients,it is recommended to bolster training specifically tailored to acute and critical care,raise awareness of first aid practices,and elevate knowledge and skill levels.

A Potential Role for GLUT4 in Predicting Sepsis in Critically Ill Children

Background: This study investigated serum Glucose transporter (GLUT) 4 levels and examined the relationship between serum GLUT4 levels and sepsis in critically ill children. Methods: This was a retrospective study of 77 critically ill children and 33 non-diabetic healthy children (controls) who were admitted between 07/2015 and 05/2016. Patient data, clinical information, and blood samples were collected on admission, alongside a large number of laboratory parameters that were routinely assessed. Critically ill patients were divided into sepsis and non-sepsis/systemic inflammatory response syndrome (SIRS). Serum GLUT4 was measured using western blotting and enzyme-linked immunosorbent assays. Insulin resistance indexes, clinical data, laboratory parameters, and inflammatory cytokines were assessed. Results: GLUT4 serum levels were higher in critically ill children than in healthy children (90.5 vs. 30.3 μg/L, P 0.05). Compared to healthy children, hyperglycemic patients (n = 48) had elevated GLUT4 serum levels (30.3 vs. 103.7 g/L, P Conclusions: GLUT4 serum levels might be significantly increased in critically ill children compared with healthy children, particularly those in septic shock. Serum GLUT4 could predict disease severity.

The Role of Grid-Style Nursing Management Model in Critically Ill Patients

Objective:This study aims to gain insight into the effects and potential advantages of the grid-style nursing management model in the care of critically ill patients.Methods:Eighty critically ill patients admitted to our hospital between May 2020 and May 2021 were selected and randomly divided into the control group and the grid group,each with 40 patients.The control group implemented traditional nursing management,while the grid group adopted a grid-style nursing management model.The quality of care,quality of life,nursing satisfaction,and treatment adherence of the two groups were compared.Results:Compared with the control group,the grid group had significantly higher quality of care and quality of life(P<0.001);in terms of nursing satisfaction,the score of the grid group was 8.26±0.85,which was significantly higher than that of the control group(6.65±0.77)(P<0.001);90.00%(36 patients)of the grid group showed good treatment adherence,significantly higher than 70.00%(28 patients)of the control group(P<0.001).Conclusion:The implementation of the grid-style nursing management model in critically ill patients can significantly improve the quality of care,quality of life,and satisfaction of patients,and effectively promote patients’treatment adherence.These positive results provide strong support for the promotion and application of this model in clinical care.

Cytomegalovirus infection in non-immunocompromised critically ill patients:A management perspective

Critically ill patients are a vulnerable group at high risk of developing secondary infections.High disease severity,prolonged intensive care unit(ICU)stay,sepsis,and multiple drugs with immunosuppressive activity make these patients prone to immuneparesis and increase the risk of various opportunistic infections,including cytomegalovirus(CMV).CMV seroconversion has been reported in up to 33%of ICU patients,but its impact on patient outcomes remains a matter of debate.Even though there are guidelines regarding the management of CMV infection in immunosuppressive patients with human immunodeficiency virus/acquired immuno deficiency syndrome,the need for treatment and therapeutic approaches in immunocompetent critically ill patients is still ambiguous.Even the diagnosis of CMV infection may be challenging in such patients due to non-specific symptoms and multiorgan involvement.Hence,a better understanding of the symptomatology,diagnostics,and treatment options may aid intensive care physicians in ensuring accurate diagnoses and instituting therapeutic interventions.

Research on the Application of Evidence-Based Quality Control Circle to Improve the Implementation Rate of Airway Management Measures in Adult Critically Ill Patients

Objective: To explore the effect of evidence-based quality control circle (QCC) in improving the implementation rate of airway management measures in adult critically ill patients. Methods: Based on the Joanna Briggs Institute (JBI) evidence-based health care model, the best evidence of airway management in adult critically ill patients was obtained and applied to the clinic. Results: The total implementation rate of airway management measures in adult critically ill patients increased from 23.62% before the implementation of quality control circle to 88.82%, and the pulmonary infection rate in critically ill patients decreased from 42.31% to 21.74%, with statistical significance between the two groups (P 0.05). Conclusion: Evidence-based quality control circle activities can standardize the practice standards of airway management in critically ill patients, reduce the occurrence of patients’ airway related complications, and improve clinical outcomes.

Nursing Experience of Early Application of Nasoenteric Tube for Enteral Nutrition in Critically Ill ICU Patients

Objective:To investigate the effective nursing measures of early application of nasoenteric tube for enteral nutrition in critically ill patients in ICU,and to summarize the nursing experience.Methods:The study was carried out in June 2023–November 2023.62 samples of ICU critically ill patients were selected,all of whom used enteral nutrition by mesenteric tube and were grouped into an observation group(n=31)and a control group(n=31)by using the numerical table randomization method.The patients in the control group were basic nursing interventions,and the patients in the observation group were comprehensive quality care,comparing the nutritional indexes,complication rates,and nursing satisfaction between the two groups.Results:All nutritional indicators of the observation group were higher than those of the control group after nursing intervention(P<0.05);the complication rate of the observation group was lower than that of the control group(P<0.05);the nursing satisfaction of the observation group was higher than that of the control group(P<0.05).Conclusion:Comprehensive quality nursing care during the early application of a gastroenteric tube for enteral nutrition in critically ill patients in the ICU can improve nutritional indexes,reduce the incidence of complications and improve nursing satisfaction.

Effects of glucocorticoids on traumatic brain injury related critical illness-related corticosteroid insufficiency

Background Traumatic brain injury （TBI） is a heterogeneous condition that can lead to critical LLLness-related corticosteroid insufficiency （CIRCI） causing a high mortality and morbidity.Glucocorticoids were widely used in the clinical management of TBI,but their benefit has been challenged in some studies and their efficacy,especially for treating CIRCI in TBI patients,remains unclear.Methods We conducted a meta-analysis of published data to determine if the controversy is related to clinical dosing and timing of glucocorticoids （GCs） application.We analyzed published reports in four databases （MEDLINE,EMBASE,the Cochrane Controlled Trials Register,and CBMdisc）.The published data were stratified into not only low-and high-dose GCs group but also short-and long-term GCs group to compare their effectiveness in improving TBI outcomes.Results We totally identified 16 reports.For low-dose patients,the pooled relative risks （RRs） for two clinical outcomes of death or a combination of death and severe disability were 0.95 （95% confidence interval （CI）：0.80 to 1.13） and 0.95 （95% CI：0.83 to 1.09）,respectively.The risks for infection and gastrointestinal bleeding were 0.85 （95% CI：0.50 to 1.45） and 0.64 （95% Cl：0.15 to 2.70）,respectively.For high-dose group,the pooled RR of death is 1.14 （95% Cl：1.06 to 1.21）.The pooled RRs for infection and gastrointestinal bleeding for the high-dose patients were 1.04 （95% CI：0.93 to 1.15） and 1.26 （95% CI：0.92 to 1.75）,respectively.For long-term use group,the pooled RRs for two clinical outcomes of death or a combination of death and severe disability were 0.98 （95% CI：0.87 to 1.12） and 1.00 （95% CI：0.90 to 1.11）,respectively.The risks for infection and gastrointestinal bleeding were 0.88 （95% CI：0.71 to 1.11） and 0.96 （95% CI：0.35 to 2.66）,respectively.For short-term use group,the pooled RR of death is 1.15 （95% CI：1.07 to 1.23）,and importantly the effects on infections were beneficial in terms of TBI patients suffering from CIRCI.Conclusions This meta-analysis suggests an increased risk of death for TBI patients on a high dose and short term of glucocorticoids compared with those on a low dose and long term,for whom a trend towards clinical improvement is evident.In addition,stress-does of GCs further decrease the pneumonia incidence in TBI patients suffering from CIRCI.A large-scale multicenter randomized controlled trial is warranted for testing （1） the efficacy of stress-dose GCs treatment in the sub-acute phase of TBI （4-21 days after initial trauma）,when CIRCI is most likely to occur; （2） the hypothesis that stress-dose GCs could boost patients＇ stress function and ensure survival.

Evaluation of a protocol for rifaximin discontinuation in critically ill patients with liver disease receiving broad-spectrum antibiotic therapy

BACKGROUND Rifaximin is frequently administered to critically ill patients with liver disease and hepatic encephalopathy,but patients currently or recently treated with antibiotics were frequently excluded from studies of rifaximin efficacy.Due to overlapping spectrums of activity,combination therapy with broad-spectrum antibiotics and rifaximin may be unnecessary.A pharmacist-driven protocol was piloted to reduce potentially overlapping therapy in critically ill patients with liver disease.It was hypothesized that withholding rifaximin during broad-spectrum antibiotic therapy would be safe and reduce healthcare costs.AIM To determine the clinical,safety,and financial impact of discontinuing rifaximin during broad-spectrum antibiotic therapy in critically ill liver patients.METHODS This was a single-center,quasi-experimental,pre-post study based on a pilot pharmacist-driven protocol.Patients in the protocol group were prospectively identified via the medical intensive care unit(ICU)(MICU)protocol to have rifaximin withheld during broad-spectrum antibiotic treatment.These were compared to a historical cohort who received combination therapy with broadspectrum antibiotics and rifaximin.All data were collected retrospectively.The primary outcome was days alive and free of delirium and coma(DAFD)to 14 d.Safety outcomes included MICU length of stay,48-h change in vasopressor dose,and ICU mortality.Secondary outcomes characterized rifaximin cost savings and protocol adherence.Multivariable analysis was utilized to evaluate the association between group assignment and the primary outcome while controlling for potential confounding factors.RESULTS Each group included 32 patients.The median number of delirium-and coma-free days was similar in the control and protocol groups[3 interquartile range(IQR 0,8)vs 2(IQR 0,9.5),P=0.93].In multivariable analysis,group assignment was not associated with a reduced ratio of days alive and free of delirium or coma at 14 d.The protocol resulted in a reduced median duration of rifaximin use during broad-spectrum antibiotic therapy[6 d control(IQR 3,9.5)vs 1 d protocol(IQR 0,1);P<0.001].Rates of other secondary clinical and safety outcomes were similar including ICU mortality and 48-h change in vasopressor requirements.Overall adherence to the protocol was 91.4%.The median estimated total cost of rifaximin therapy per patient was reduced from$758.40(IQR$379.20,$1200.80)to$126.40(IQR$0,$126.40),P<0.01.CONCLUSION The novel pharmacist-driven protocol for rifaximin discontinuation was associated with significant cost savings and no differences in safety outcomes including DAFD.