Background:Fluid is an essential component of initial resuscitation in sepsis or burns. Meanwhile, the optimal strategy of titrating fluids for both of the two conditions remains uncertain. In this bibliometric analysis, we compared the similarities and differences in fluid resuscitation between sepsis and burns in recent publications. Methods:Literatures related to fluid resuscitation in either sepsis or burns were searched in the Web of Science database Core Collection from January 1, 1992, to December 31, 2022. CiteSpace and VOSviewer was used for bibliometric analysis. Results:A total of 1,549 and 468 publications on fluid resuscitation in sepsis and burns were retrieved from 1992 to 2022. Based on the occurrences, 341 and 86 high-frequency keywords were screened out from sepsis and burns publications, respectively, which were similarly categorized into 5 clusters [i.e. "mechanisms of hypovolemia" (cluster 1), "titration of fluid" (cluster 2), "outcomes or complications" (cluster 3), "pathophysiological alternations" (cluster 4), and "fluid types and others" (cluster 5)]. The high-frequency keywords of the top 20 were more concentrated in cluster 3 and cluster 2, with "mortality" ranked the top in both sepsis and burns literature. Significantly, 3 keywords in cluster 2 ranked in the top 5, including "goal directed resuscitation" (the 3rd), fluid responsiveness (the 4th) and fluid balance (the 5th) in sepsis literature, while the keywords of "microvascular exchange" (cluster 1) and "abdominal compartment syndrome" (ACS, cluster 3) ranked at the second and the fifth place in burns publications. Keyword burst analysis demonstrated that the keyword with the highest burst strength (BS) was "formula" (BS = 5.88, 2008-2014), followed by management (BS = 4.79, 2012-2022), ACS (BS = 4.76, 2006-2010), and fluid creep (BS = 4.74, 2011-2016) in burn publications, but they were dobutamine (BS = 12.31, 1992-2008), cardiac output (BS = 9.79, 1993-2001), catecholamine (BS = 9.54, 1993-2006), and consumption (BS = 7.52, 1992-2006) in sepsis literature. Moreover, the most frequently cited article in either sepsis or burns was categorized into cluster 2, that investigated goal-directed fluid therapy for sepsis and formula improvement for burns resuscitation. Conclusion:It was demonstrated that the research priorities in titrating fluid were mainly concentrated on targeting hemodynamics in sepsis vs. improving formula (which briefly calculates the increased microvascular permeability) in burns, while concerning of "outcomes and complications" in fluid resuscitation similarly after 1992. However, hemodynamics and microvascular permeability have been simultaneously well considered in few previous studies regarding fluid resuscitation in either sepsis or burns.

OBJECTIVE:To investigate phenotypic classification based on plasma lactate trajectories and its association with 28-day mortality in patients with septic cardiomyopathy (SCM). METHODS:A multicenter retrospective cohort study was conducted. Patients with SCM admitted to the intensive care units (ICUs) of three tertiary hospitals (Affiliated Hospital of Guizhou Medical University, Guizhou Provincial People's Hospital, and GuiQian International Hospital) from October 2019 to December 2024 were enrolled. Baseline characteristics, intervention strategies, and clinical outcomes were collected, including the first blood lactate level upon ICU admission and daily lactate values within 7 days after SCM diagnosis. The primary outcome was 28-day mortality, and secondary outcomes included 28-day vasoactive drug-free days, duration of mechanical ventilation, and ICU length of stay. Latent class growth model (LCGM) was used to identify lactate trajectory-based phenotypes. Differences in the above indicators among phenotypes were compared, and univariate and multivariate Cox regression analyses were performed to identify independent risk factors for 28-day mortality in SCM patients. RESULTS:A total of 216 SCM patients were included, among whom 41 died and 175 survived within 28 days. LCGM identified four lactate trajectory phenotypes: phenotype 1 (persistent low level, n = 142), phenotype 2 (moderate level with rapid decline, n = 32), phenotype 3 (moderate level with slow increase, n = 20), and phenotype 4 (high level with slow decline, n = 22). The 28-day mortality rates of patients in phenotypes 1-4 showed a significant increasing trend (9.2%, 21.9%, 30.0%, and 68.2%, respectively, P < 0.05). Phenotype 1, which exhibited the lowest mortality and lowest acute physiology and chronic health evaluation (APACHE), was designated as the baseline group. Univariate Cox regression analysis showed that phenotypes 3 and 4 were associated with 28-day mortality in SCM patients (both P < 0.05). Multivariate Cox regression analysis revealed that phenotype 3 [hazard ratio (HR) = 2.831, 95% confidence interval (95%CI) was 1.243-6.447] and phenotype 4 (HR = 2.389, 95%CI was 1.223-4.663) were independent risk factors for 28-day mortality (both P < 0.05). Kaplan-Meier survival curves showed that the survival probability gradually flattened after 3 weeks of hospitalization. Using phenotype 1 as the baseline, patients with phenotypes 3 and 4 had a higher risk of death, and the risk in phenotype 4 was significantly higher than that in phenotype 3 (P < 0.05). Accordingly, the four patient groups were stratified into high-risk (high level with slow decline), intermediate-risk (moderate level with slow increase), and low-risk (moderate level with rapid decline and persistent low level) categories. CONCLUSIONS:Four phenotypes of SCM were successfully identified based on lactate trajectories, which were closely associated with 28-day mortality and could be used for risk stratification, providing new insights for prognosis assessment and individualized treatment of SCM.

BackgroundSome cohort studies have explored the effects and safety of polymyxin B (PMB) in comparison to other antibiotics for the treatment of nosocomial infections, yielding inconsistent results. This systematic review aims to explore the effectiveness and safety of PMB and compared it with other antibiotics.MethodsA systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and Web of Science, searching specific terms to identify quantitative cohort studies or RCTs that compared the effects of PMB with other antibiotics in terms of their efficacy and safety. The Newcastle–Ottawa Scale (NOS) was conducted to evaluate the risk of bias of observational studies. Odds ratios with 95% confidence intervals were used for outcome assessment. We evaluated heterogeneity using the I2 test.ResultsA total of 22 observational trials were included in the analysis. The PMB group had a higher mortality rate compared to the control group (odds ratio: 1.84, 95% CI: 1.36–2.50, p<0.00001, I2 = 73%). while, the ceftazidime-avibactam group demonstrated a distinct advantage with lower mortality rates, despite still exhibiting high heterogeneity (odds ratio 2.73, 95% confidence interval 1.59–4.69; p = 0.0003; I2 = 53%). Additionally, the PMB group had a lower nephrotoxicity rate compared to the colistin group but exhibited high heterogeneity in the results (odds ratio 0.58, 95% CI 0.36–0.93; p = 0.02; I2 = 73%).ConclusionIn patients with nosocomial infections, PMB is not superior to other antibiotics in terms of mortality, specifically when compared to ceftazidime-avibactam. However, PMB demonstrated an advantage in terms of nephrotoxicity compared to colistin.

Background and aims: Nutrition therapy is a vital part of the management of critically ill patients. Efforts have been made to optimize nutrition therapy in the ICU setting, and it is argued that protein might be the most important substrate to deliver during critical illness. However, the impact of protein delivery on patient-centered outcomes, including short-term and long-term outcomes, is controversial. Moreover, previous studies showed that compliance with the guidelines is poor in practice, and the amounts of protein intake vary significantly among different hospitals. The objective of this study is to describe the current practice of protein delivery for critically ill patients and to investigate the association between different protein delivery amounts and approaches during ICU admission and multiple patient-centered outcomes (short-term and long-term). Methods: This is a multicenter, prospective, observational study conducted in 70 hospitals, aiming to recruit more than 1800 newly admitted critically ill patients who are expected to stay in ICU for at least 48 h. Data, including the baseline characteristics, illness severity scores, requirements of organ support therapy, and daily nutritional therapy, will be recorded until day 28 after enrollment unless discharge from the ICU or death occurs first. The key long-term clinical outcomes, like readmission post the index discharge and health-related quality of life, will be collected via telephone contact on Day 90 and Day 180 after recruitment. Quality of life will be assessed by the EuroQol five dimensions five-level questionnaire (EQ5D5L) visual analogue scale score. Apart from descriptive data, multivariate analyses adjusted for potential confounders will be applied to assess the association between protein intake during ICU stay and short-term and long-term clinical outcomes.

Background Immune-enhancing thymosin alpha 1 (T alpha 1) therapy may reduce infected pancreatic necrosis (IPN) in acute necrotising pancreatitis (ANP). However, the efficacy might be impacted by lymphocyte count due to the pharmacological action of T alpha 1. In this post-hoc analysis, we tested the hypothesis that pre-treatment absolute lymphocyte count (ALC) determines whether patients with ANP benefit from T alpha 1 therapy. Methods A post-hoc analysis of data from a multicentre, double-blind, randomised, placebo-controlled trial testing the efficacy of T alpha 1 therapy in patients with predicted severe ANP was performed. Patients from 16 hospitals of China were randomised to receive a subcutaneous injection of T alpha 1 1.6 mg every 12 h for the frst 7 days and 1.6 mg once a day for the following 7 days or a matching placebo during the same period. Patients who discontinued the T alpha 1 regimen prematurely were excluded. Three subgroup analyses were conducted using the baseline ALC (at randomisation), and the group allocation was maintained as intention-to-treat. The primary outcome was the incidence of IPN 90 days after randomisation. The fitted logistic regression model was applied to identify the range of baseline ALC where T alpha 1 therapy could exert a maximum effect. The original trial is registered with ClinicalTrials.gov, NCT02473406. Findings Between March 18, 2017, and December 10, 2020, a total of 508 patients were randomised in the original trial, and 502 were involved in this analysis, with 248 in the T alpha 1 group and 254 in the placebo group. Across the three subgroups, there was a uniform trend toward more significant treatment effects in patients with higher baseline ALC. Within the subgroup of patients with baseline ALC >= 0.8 x 10 boolean AND 9/L (n = 290), the T alpha 1 therapy significantly reduced the risk of IPN (covariate adjusted risk difference, -0.12; 95% CI, -0.21,-0.02; p = 0.015). Patients with baseline ALC between 0.79 and 2.00 x 10 boolean AND 9/L benefited most from the T alpha 1 therapy in reducing IPN (n = 263). Interpretation This post-hoc analysis found that the efficacy of immune-enhancing T alpha 1 therapy on the incidence of IPN may be associated with pretreatment lymphocyte count in patients with acute necrotising pancreatitis. Funding National Natural Science Foundation of China. 2023;58: 2023

BackgroundWe have updated the guideline for preventing and managing perioperative infection in China, given the global issues with antimicrobial resistance and the need to optimize antimicrobial usage and improve hospital infection control levels. MethodsWe conducted a comprehensive evaluation of the evidence for prevention and management of perioperative infection, based on the concepts of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The strength of recommendations was graded and voted using the Delphi method and the nominal group technique. Revisions were made to the guidelines in response to feedback from the experts. ResultsThere were 17 questions prepared, for which 37 recommendations were made. According to the GRADE system, we evaluated the body of evidence for each clinical question. Based on the meta-analysis results, recommendations were graded using the Delphi method to generate useful information. ConclusionsThis guideline provides evidence to perioperative antimicrobial prophylaxis that increased the rational use of prophylactic antimicrobial use, with substantial improvement in the risk-benefit trade-off.

BackgroundAlthough publications have been increasing rapidly, the research quality has yet to improve in the field of critical care medicine (CCM) in China. This study aimed at investigating the current status of and the influential factors for impactful publications in CCM research by Chinese authors.MethodsPublications by authors with the affiliation of critical care medicine department or intensive care unit (CCM/ICU) in Chinese as well as American hospitals from 2001 to 2020 were retrieved from the Web of Science Core Collection (WoSCC) database for this bibliometric analysis. Moreover, statistical analyses to test factors affecting impactful publications by Chinese authors were performed.ResultsOf 13,487 articles retrieved by this search strategy, 6,622 were published by Chinese authors as first or corresponding authors. The annual publications by Chinese authors have been rapidly increasing from 2001 to 2020, and so did the citations to these articles. However, the proportion in the world of publications by Chinese authors was much less than that by American authors each year [M (IQR): 1.85 (9.592) vs. 27.77 (7.3), p < 0.001]. In addition, impactful articles were significantly less published by Chinese than by American authors, including articles either in journals with a high impact factor (p < 0.001) or in the top 10 journals in the field of CCM (5.4 vs 13.4%, p < 0.001), and articles with high citation frequency as well (p < 0.001). Moreover, the percentage of impactful publications by Chinese authors was likely associated with academic background and regions of the author's affiliations, funds support, public health events of COVID-19, and collaboration between authors.ConclusionOur results demonstrated that CCM research in China grew rapidly in the recent 20 years. However, the impactful publications remained limited, largely owing to the shortage of comprehensive research training, inactive collaboration, and underfunded CCM research.

PurposeThe study aimed to explore factors associated with deep sedation practice in intensive care units (ICUs).Materials and MethodsA post hoc analysis was conducted for a cross–sectional survey on sedation practices in mechanically ventilated (MV) patients, combined with a questionnaire for physicians regarding their preferences for light sedation (P–pls Score) in 92 Chinese ICUs.ResultsThere were 457 and 127 eligible MV patients in the light and deep sedation groups respectively. A multivariable logistic regression analysis demonstrated that the control mode of mechanical ventilation, plasma lactate level, and the Sequential Organ Failure Assessment (SOFA) score were independent risk factors for deep sedation practice (p <0.01). Notably, the adjusted odds ratio (95% CI) of the average P–pls score in the ICU ≤ 2 for deep sedation practice was 1.861 (1.163, 2.978, p = 0.01). In addition, the areas under curves of receiver operating characteristics (AUC–ROC) of the model to predict the probability of deep sedation practice were 0.753 (0.699, 0.806) and 0.772 (0.64, 0.905) in the training set and the validation set, respectively. The 28–day mortality was increased in patients with exposure to deep sedation practice but not significantly.ConclusionBoth factors related to stressful stimuli and the ICU physicians' perception of patient tolerability in mechanical ventilation were likely associated with deep sedation practice in MV patients.

Endothelial dysfunction is a primary pathophysiological change in sepsis. Macrophages are known to interact with vascular endothelial cells during the development of sepsis. Recently, drug delivery based on engineered macrophages was reported as an alternative approach for the management of diseases. Interleukin‐10 (IL10) is a well‐known anti‐inflammatory cytokine, which reduces inflammation and inhibits dysfunction of endothelial cells caused by sepsis. It is currently poorly understood whether genetically modified macrophages with overexpression of IL10 are able to restore endothelial integrity and function at the cellular level. In this study, we used lentiviral vectors to construct RAW264.7 macrophages engineered to overexpress IL10 (IL10‐eM) and investigated the effects of the IL10‐eM supernatant on LPS‐induced endothelial dysfunction using a noncontact coculture system. We found that cotreatment with IL10‐eM supernatant significantly attenuates the effects of LPS‐induced dysfunction of endothelial cells, including endothelial inflammatory response, endothelial permeability, and apoptosis. In addition, we discovered that LPS‐induced downregulation of VE‐cadherin and high production of reactive oxygen species were significantly attenuated upon IL10‐eM exposure. Furthermore, upregulation of IL6, TNFα, and Bax was decreased after treatment of cells with IL10‐eM supernatant. These results demonstrated that supernatant from engineered macrophages genetically modified with IL10 can effectively protect endothelial cells against LPS‐induced dysfunction in vitro, suggesting that exosomes from such engineered macrophages may have therapeutic effects against sepsis.

OBJECTIVES: Light sedation is recommended over deep sedation for invasive mechanical ventilation to improve clinical outcome but may increase the risk of agitation. This study aimed to develop and prospectively validate an ensemble machine learning model for the prediction of agitation on a daily basis. DESIGN: Variables collected in the early morning were used to develop an ensemble model by aggregating four machine learning algorithms including support vector machines, C5.0, adaptive boosting with classification trees, and extreme gradient boosting with classification trees, to predict the occurrence of agitation in the subsequent 24 hours. SETTING: The training dataset was prospectively collected in 95 ICUs from 80 Chinese hospitals on May 11, 2016, and the validation dataset was collected in 20 out of these 95 ICUs on December 16, 2019. PATIENTS: Invasive mechanical ventilation patients who were maintained under light sedation for 24 hours prior to the study day and who were to be maintained at the same sedation level for the next 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 578 invasive mechanical ventilation patients from 95 ICUs in 80 Chinese hospitals, including 459 in the training dataset and 119 in the validation dataset, were enrolled. Agitation was observed in 36% (270/578) of the invasive mechanical ventilation patients. The stepwise regression model showed that higher body temperature (odds ratio for 1°C increase: 5.29; 95% CI, 3.70–7.84; p < 0.001), greater minute ventilation (odds ratio for 1 L/min increase: 1.15; 95% CI, 1.02–1.30; p = 0.019), higher Richmond Agitation-Sedation Scale (odds ratio for 1-point increase: 2.43; 95% CI, 1.92–3.16; p < 0.001), and days on invasive mechanical ventilation (odds ratio for 1-d increase: 0.95; 95% CI, 0.93–0.98; p = 0.001) were independently associated with agitation in the subsequent 24 hours. In the validation dataset, the ensemble model showed good discrimination (area under the receiver operating characteristic curve, 0.918; 95% CI, 0.866–0.969) and calibration (Hosmer-Lemeshow test p = 0.459) in predicting the occurrence of agitation within 24 hours. CONCLUSIONS: This study developed an ensemble model for the prediction of agitation in invasive mechanical ventilation patients under light sedation. The model showed good calibration and discrimination in an independent dataset.

Causal inference research is a causal test designed to assess the impact of exposures on outcomes.Both experimental and observational studies can be used to examine causal associations between exposure factors and outcomes. Experimental studies are sometimes limited by factors such as ethics or experimental conditions. Observational studies account for a large proportion in clinical studies, but the effectiveness and research value of observational studies will be affected if the design of observational studies is not rigorous and the confounding factors are not well controlled.The Guidelines for controlling confounding factors and reporting results in causal inference studie formulated by a special group of 47 editors from 35 journals from all over the world provide good guidance to researchers. This article interprets the guidelines and hopes to provide help for clinical researchers.

BACKGROUND:Septic shock comprises a heterogeneous population, and individualized resuscitation strategy is of vital importance. The study aimed to identify subclasses of septic shock with non-supervised learning algorithms, so as to tailor resuscitation strategy for each class.METHODS:Patients with septic shock in 25 tertiary care teaching hospitals in China from January 2016 to December 2017 were enrolled in the study. Clinical and laboratory variables were collected on days 0, 1, 2, 3 and 7 after ICU admission. Subclasses of septic shock were identified by both finite mixture modeling and K-means clustering. Individualized fluid volume and norepinephrine dose were estimated using dynamic treatment regime (DTR) model to optimize the final mortality outcome. DTR models were validated in the eICU Collaborative Research Database (eICU-CRD) dataset.RESULTS:A total of 1437 patients with a mortality rate of 29% were included for analysis. The finite mixture modeling and K-means clustering robustly identified five classes of septic shock. Class 1 (baseline class) accounted for the majority of patients over all days; class 2 (critical class) had the highest severity of illness; class 3 (renal dysfunction) was characterized by renal dysfunction; class 4 (respiratory failure class) was characterized by respiratory failure; and class 5 (mild class) was characterized by the lowest mortality rate (21%). The optimal fluid infusion followed the resuscitation/de-resuscitation phases with initial large volume infusion and late restricted volume infusion. While class 1 transitioned to de-resuscitation phase on day 3, class 3 transitioned on day 1. Classes 1 and 3 might benefit from early use of norepinephrine, and class 2 can benefit from delayed use of norepinephrine while waiting for adequate fluid infusion.CONCLUSIONS:Septic shock comprises a heterogeneous population that can be robustly classified into five phenotypes. These classes can be easily identified with routine clinical variables and can help to tailor resuscitation strategy in the context of precise medicine.

Background: The role of sodium bicarbonate therapy (SBT) remains controversial. This study aimed to investigate whether hemodynamic status before SBT contributed to the heterogeneous outcomes associated with SBT in acute critically ill patients. Methods: We obtained data from patients with metabolic acidosis from the Medical Information Mart for Intensive Care (MIMIC)-III database. Propensity score matching (PSM) was applied to match the SBT group with the control group. Logistic regression and Cox regression were used to analyze a composite of newly “developed or exacerbated organ dysfunction” (d/eOD) within 7 days of ICU admission and 28-day mortality associated with SBT for metabolic acidosis. Results: A total of 1,765 patients with metabolic acidosis were enrolled, and 332 pairs obtained by PSM were applied to the final analyses in the study. An increased incidence of newly d/eOD was observed in the SB group compared with the control group (54.8 vs. 44.6%, p < 0.01). Multivariable logistic regression indicated that the adjusted OR of SBT for this composite outcome was no longer significant [OR (95% CI): 1.39 (0.9, 1.85); p = 0.164]. This effect of SBT did not change with the quintiles stratified by pH. Interestingly, SBT was associated with an increased risk of the composite of newly d/eOD in the subgroup of patients with worsening hemodynamics before SBT [adjusted OR (95% CI): 3.6 (1.84, 7.22), p < 0.001]. Moreover, the risk potential for this composite of outcomes was significantly increased in patients characterized by both worsening [adjusted OR (95% CI): 2.91 (1.54, 5.47), p < 0.001] and unchanged hemodynamics [adjusted OR (95% CI): 1.94 (1.01, 3.72), p = 0.046] compared to patients with improved hemodynamics before SBT. Our study failed to demonstrate an association between SBT and 28-day mortality in acute critically ill patients with metabolic acidosis. Conclusions: Our findings did not demonstrate an association between SBT and outcomes in critically ill patients with metabolic acidosis. However, patients with either worsening or unchanged hemodynamic status in initial resuscitation had a significantly higher risk potential of newly d/eOD subsequent to SBT.

© The Author(s) 2021. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/bync/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Burns & Trauma, 2021, 9, tkab006 doi: 10.1093/burnst/tkab006 Letter to the Editor

Suboptimal sedation practices continue to be frequent, although the updated guidelines for management of pain, agitation, and delirium in mechanically ventilated (MV) patients have been published for several years. Causes of low adherence to the recommended minimal sedation protocol are multifactorial. However, the barriers to translation of these protocols into standard care for MV patients have yet to be analyzed. In our view, it is necessary to develop fresh insights into the interaction between the patients' responses to nociceptive stimuli and individualized regulation of patients' tolerance when using analgesics and sedatives. By better understanding this interaction, development of novel tools to assess patient pain tolerance and to define and predict oversedation or delirium may promote better sedation practices in the future.

Renal artery aneurysm (RAA) rupture during pregnancy is an extremely rare emergency with a high mortality rate for both mother and fetus. A timely diagnosis is crucial for management of RAA rupture. However, lack of typical clinical manifestations of RAA rapture often lead to a diagnosis delay or even misdiagnosis. Significantly, diagnoses of RAA rupture is more complex in laboring owing to labor pain, that therefore becomes a big challenge for clinicians. Up to now, RAA rupture in labor has been rarely reported. This paper reports a case occurred in laboring largely but diagnosed delay in postpartum, and analyzes the key points for timely diagnosis and management strategies of RAA rupture in labor through systematic literature review.

To the Editor: Anemia is a common finding among patients admitted to intensive care units (ICUs), nearly 60% of ICU patients had serum hemoglobin levels <12 g/dL at baseline, 30% of whom had serum hemoglobin levels <9 g/dL, over 95% of critically ill patients were anemic within 3 days of ICU admission.[1] Moreover, anemia may be aggravated or newly developed in critically ill patients during their ICU stay. Severe anemia could result in a decline in oxygen delivery, and hence, it may affect heart, kidney, metabolic pathway, and brain function among critically ill patients.[2] As a result, anemia could be associated with worse outcomes during critical illnesses. The role of anemia in the prognosis of critically ill patients remains debated. While anemia has been reported to be associated with prolonged length of ICU or hospital stay and increased mortality rate among critically ill patients suffering from sepsis, cardiogenic shock, or trauma in some studies, in some other investigations these outcomes were not observed in patients with chronic obstructive pulmonary disease (COPD), cancer, and burn casualties. Therefore, we hypothesize that the effect of anemia on outcomes could vary in subgroups of critically ill patients based on primary diseases, and it is plausible that the pathogenesis of anemia may influence the prognosis of critically ill patients. Hence, we conducted a meta-analysis to find the relationship between anemia, either as a comorbid condition or a consequence of critical illness, and clinical outcomes to test this hypothesis. We performed an electronic search in PubMed, Web of Science, and EMBASE from inception to September 2020 (Supplementary Digital Content, 1, https://links.lww.com/CM9/A708). We included cohort and case-control studies to investigate the association between anemia and ICU outcomes. Patients ≥18 years old who were admitted to the ICU were included. Anemia was defined as serum hemoglobin level <13 mg/dL in men and <12 mg/dL in women at entry or during the ICU stay. We excluded studies without an abstract, or those written in other languages other than English or Chinese. The outcomes of interest included mortality, length of ICU and hospital stay, and complications related to anemia. For all-cause mortality, we conducted subgroup analyses based on primary diagnoses in the ICU. Two reviewers screened the English and Chinese language search results independently. Any disagreement was resolved by discussion with a third author. As a result, the electronic search yielded 3357 references. Ultimately, 28 studies (included eight case-control studies and 20 cohort studies) with a total of 28,285 patients were included in the final systematic review [Supplementary Digital Content, Table 1, https://links.lww.com/CM9/A708]. The study population was comprised of ICU admissions with diagnoses post-surgery, stroke, neoplasm, septic shock, hypovolemic shock, respiratory failure, cardiogenic shock, acute kidney injury, severe burns, COPD, cancer, severe brain injury, trauma, sepsis, and postoperative peritonitis. All studies had a high risk of bias. One of the major sources of bias was the type of study participants. Most studies only included patients with a specific disease, therefore, they could not represent all ICU patients. Also, anemia definition was different among studies [Supplementary Digital Content, Table 2, https://links.lww.com/CM9/A708]. Seventeen studies (15,499 participants, 54.7%) reported the association between anemia and all-cause mortality. Fourteen studies (15,167 participants, 54%) used odds ratio (OR) as the measurement of the association. In univariate analysis of pooled data, anemia was found to be associated with an increased risk of death. This was particularly noted in 11 out of 14 studies (10,060 participants, 39%) with OR of 2.57 and 95% confidence interval (CI) of 1.94–3.40, I2 = 63% [Figure 1]. Four out of seventeen studies underwent multivariate analysis after adjusting for baseline characteristics. The results yielded a nonsignificant association between anemia and all-cause mortality (adjusted OR: 1.36, 95% CI 0.73–2.52, I2 = 75%) [Figure 1].Figure 1: Forest plots representing anemia and all-cause mortality by odds ratio. Han 2015: adjusted factors included age, sex, body weight, systolic/diastolic blood pressure, primary diagnosis, chronic kidney disease, diabetes mellitus, non-hematologic/hematologic malignancy, previously diagnosed anemia, bleeding, need for mechanical ventilation, use of vasoactive and nonsteroidal anti-inflammatory drugs (NSAID), contrast media, and APACHE II score. Kopterides 2011: adjusted factors included simplified acute physiology score, performance status, septic shock on admission. Okoye 2013: adjusted factors included gender, mean hemoglobin on admission, coagulopathy on admission, head abbreviated injury score, injury severity score, packed red blood cells transfusion, packed red blood cells units, fresh frozen plasma units, platelet units, cryoprecipitate units. Salim 2008: adjusted factors included transfusion, anemia and transfusion interaction, head abbreviated injury score, age, gender, injury severity score, head injury, spinal column injury, systolic blood pressure, heart rate. SE: Standard error; CI: Confidence interval.Subgroup analyses for patients with acute kidney injury, trauma, cancer, and peritonitis, sepsis, and those admitted in cardiac intensive care units showed anemia to be associated with a higher risk of all-cause mortality. This association was not observed for patients with traumatic brain injury [Supplementary Digital Content, Figure 4A–D, https://links.lww.com/CM9/A708]. We investigated the effect of anemia on ICU- and hospital-related mortality as well as mortality at 30-day, 90-day, and 6 years follow-ups. The association between anemia and ICU mortality was reported in two studies involving 1158 (4%) participants. The univariate analysis showed a nonsignificant association between anemia and ICU mortality (OR: 1.78, 95% CI: 0.61–5.18, I2 = 66%), while multivariate analysis in one study involving 126 (0.4%) participants indicated that anemia was significantly associated with an increased odds of ICU mortality (OR: 4.06, 95% CI: 1.30–12.68) [Supplementary Digital Content, Figure 5A, https://links.lww.com/CM9/A708]. Subgroup analysis showed that among patients with COPD and cancer, there was no association between anemia and ICU mortality [Supplementary Digital Content, Figure 5B, https://links.lww.com/CM9/A708]. Four studies including 1967 participants (7%) reported the association between anemia and hospital mortality. These studies demonstrated a significantly increased pooled OR of 2.22 (95% CI: 1.39–3.56, I2 = 69%) of hospital mortality among anemic patients. In a multivariate analysis, one study, including 2807 (10%) participants, observed a significantly decreased risk of hospital death per unit increase in hemoglobin (OR: 0.89, 95% CI: 0.82–0.97) [Supplementary Digital Content, Figure 5C], https://links.lww.com/CM9/A708. Subgroup analysis showed patients in the cardiac ICU or those with peritonitis had a higher risk of hospital mortality when they were anemic [Supplementary Digital Content, Figure 5D, https://links.lww.com/CM9/A708]. However, for patients with COPD, there was no association between anemia and hospital mortality. Two studies revealed that anemic patients had a significantly higher risk of 30-day mortality (RR: 3.10, 95% CI: 1.63–5.90; RR: 1.79, 95% CI: 1.08–2.97). The risk of 90-day mortality in patients with anemia was found to be significantly higher than those without anemia (RR: 2.60, 95% CI: 1.50–4.5 and HR: 1.68, 95% CI: 1.03–2.74). In 1 study involving 2145 participants (8%), a significant increase in 6-year mortality was observed among patients with anemia compared with the control population (OR: 1.79, 95% CI: 1.49–2.13). Two studies showed there was no significant association between anemia and length of mechanical ventilation, ICU, or hospital stay. While one study revealed that patients with anemia had a significantly longer ICU stay (MD: 8.0, 95% CI: 5.93–10.07, Supplementary Digital Content, Table 3, https://links.lww.com/CM9/A708). There was no significant association between anemia and progression of acute kidney injury (AKI) from stage I to III [Supplementary Digital Content, Table 3, https://links.lww.com/CM9/A708]. A significantly increased risk of AKI in patients with anemia was found in one study involving 2145 (12.02%) participants (HR: 1.76, 95% CI: 1.35–2.30); however, this was nonsignificant at six months follow-up based on another study [Supplementary Digital Content, Figure 2, https://links.lww.com/CM9/A708]. We assessed the reporting bias through visual interpretation of funnel plots only for all-cause mortality using univariate analysis [Supplementary Digital Content, Figure 3, https://links.lww.com/CM9/A708], and did not find reporting biases. We did not assess the reporting bias for the other outcomes included less than 10 studies, due to the low test efficiency. In this study, we reported the results of a meta-analysis to examine the association between anemia and clinical outcomes. Our data indicate an increased risk of all-cause mortality in patients with anemia compared with a non-anemic population. In addition, patients with anemia in the ICU were more likely to develop AKI. Subgroup analyses showed that for patients with AKI, trauma, cancer, sepsis, and patients in the cardiac ICU, anemia was associated with a higher risk of all-cause mortality. However, this association was not observed among patients with traumatic brain injury. There was also no association between anemia with ICU mortality among COPD or cancer patients. Unlike patients with COPD, patients in the cardiac ICU or those with peritonitis had a higher risk of hospital mortality when they were anemic. Anemia is a clinically relevant issue, commonly due to abnormal response to erythropoietin, iron or other vitamin deficiencies, inflammation or infection, hemorrhage, hemolysis, and frequent blood draws in ICUs.[3] Severe anemia could result in oxygen delivery and consumption mismatch, particularly within organs that primarily rely on oxidative metabolisms such as the kidney tubular epithelial and myocardial cells.[4] Renal tubular cells have limited glycolytic capacity, which increases their dependency on the maintenance of appropriate renal blood flow.[5] Our data support the relationship between anemia and its physiological function on several organs which could lead to higher mortality. There is no well-known mechanism to explain the association between anemia and mortality in ICU patients. Further research is required to characterize underlying mechanisms that explain our observed associations between anemia and higher mortality rates based on differences in underlying pathologies and injuries. In conclusion, anemia among critically ill patients may be associated with a higher risk of mortality, it also could be more correlated with a higher incidence of complications, such as acute kidney injury. In the future, the occurrence of anemia at different time-points in relation to ICU admission, as well as degree and occurrence rate of anemia, duration of anemia, and whether blood transfusion should also be measured and recorded in future studies. Acknowledgments The authors thank Prof. Kianoush B. Kashani for the review. Conflicts of interest None.

The management of healthcare services for the suspected cases in non-designated hospitalsis a serious concern in controlling coronavirus disease 2019 (COVID-19) epidemic. Owing to the complexity of care providers, large requirement of medical supplies as well as the possible needs off frequent transfers, the major difficulty is preventing the coronavirus from spreading while caring the suspected critical cases before the 2019 novel coronavirus ribonucleic acid test results are reported. For the purpose of enhancing the prevention of the propagation of COVID-19, this article puts emphasis on the following aspects in non-designated hospital Peking University Third Hospital: preparatory procedures of receiving critical suspected patients, the management of medical personnel during the waiting session of RNA test results, the delivering procedures of testing samples, the management of referred medical wastes, daily operations including the cleaning and sanitizing of caring units and the management of related patients after the testing session.