Showing papers in "Journal of intensive care in 2020"

Lymphopenia in severe coronavirus disease-2019 (COVID-19): Systematic review and meta-analysis

Abstract: Clinical and laboratory biomarkers to predict the severity of coronavirus disease 2019 (COVID-19) are essential in this pandemic situation of which resource allocation must be urgently prepared especially in the context of respiratory support readiness. Lymphocyte count has been a marker of interest since the first COVID-19 publication. We conducted a systematic review and meta-analysis in order to investigate the association of lymphocyte count on admission and the severity of COVID-19. We would also like to analyze whether patient characteristics such as age and comorbidities affect the relationship between lymphocyte count and COVID-19. Comprehensive and systematic literature search was performed from PubMed, SCOPUS, EuropePMC, ProQuest, Cochrane Central Databases, and Google Scholar. Research articles in adult patients diagnosed with COVID-19 with information on lymphocyte count and several outcomes of interest, including mortality, acute respiratory distress syndrome (ARDS), intensive care unit (ICU) care, and severe COVID-19, were included in the analysis. Inverse variance method was used to obtain mean differences and its standard deviations. Maentel-Haenszel formula was used to calculate dichotomous variables to obtain odds ratios (ORs) along with its 95% confidence intervals. Random-effect models were used for meta-analysis regardless of heterogeneity. Restricted-maximum likelihood random-effects meta-regression was performed for age, gender, cardiac comorbidity, hypertension, diabetes mellitus, COPD, and smoking. There were a total of 3099 patients from 24 studies. Meta-analysis showed that patients with poor outcome have a lower lymphocyte count (mean difference − 361.06 μL [− 439.18, − 282.95], p < 0.001; I2 84%) compared to those with good outcome. Subgroup analysis showed lower lymphocyte count in patients who died (mean difference − 395.35 μL [− 165.64, − 625.07], p < 0.001; I2 87%), experienced ARDS (mean difference − 377.56 μL [− 271.89, − 483.22], p < 0.001; I2 0%), received ICU care (mean difference − 376.53 μL [− 682.84, − 70.22], p = 0.02; I2 89%), and have severe COVID-19 (mean difference − 353.34 μL [− 250.94, − 455.73], p < 0.001; I2 85%). Lymphopenia was associated with severe COVID-19 (OR 3.70 [2.44, 5.63], p < 0.001; I2 40%). Meta-regression showed that the association between lymphocyte count and composite poor outcome was affected by age (p = 0.034). This meta-analysis showed that lymphopenia on admission was associated with poor outcome in patients with COVID-19.

D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: A case control study

Abstract: Over 5,488,000 cases of coronavirus disease-19 (COVID-19) have been reported since December 2019. We aim to explore risk factors associated with mortality in COVID-19 patients and assess the use of D-dimer as a biomarker for disease severity and clinical outcome. We retrospectively analyzed the clinical, laboratory, and radiological characteristics of 248 consecutive cases of COVID-19 in Renmin Hospital of Wuhan University, Wuhan, China from January 28 to March 08, 2020. Univariable and multivariable logistic regression methods were used to explore risk factors associated with in-hospital mortality. Correlations of D-dimer upon admission with disease severity and in-hospital mortality were analyzed. Receiver operating characteristic curve was used to determine the optimal cutoff level for D-dimer that discriminated those survivors versus non-survivors during hospitalization. Multivariable regression that showed D-dimer > 2.0 mg/L at admission was the only variable associated with increased odds of mortality [OR 10.17 (95% CI 1.10–94.38), P = 0.041]. D-dimer elevation (≥ 0.50 mg/L) was seen in 74.6% (185/248) of the patients. Pulmonary embolism and deep vein thrombosis were ruled out in patients with high probability of thrombosis. D-dimer levels significantly increased with increasing severity of COVID-19 as determined by clinical staging (Kendall’s tau-b = 0.374, P = 0.000) and chest CT staging (Kendall’s tau-b = 0.378, P = 0.000). In-hospital mortality rate was 6.9%. Median D-dimer level in non-survivors (n = 17) was significantly higher than in survivors (n = 231) [6.21 (3.79–16.01) mg/L versus 1.02 (0.47–2.66) mg/L, P = 0.000]. D-dimer level of > 2.14 mg/L predicted in-hospital mortality with a sensitivity of 88.2% and specificity of 71.3% (AUC 0.85; 95% CI = 0.77–0.92). D-dimer is commonly elevated in patients with COVID-19. D-dimer levels correlate with disease severity and are a reliable prognostic marker for in-hospital mortality in patients admitted for COVID-19.

Molecular diversity of extended-spectrum β-lactamases and carbapenemases, and antimicrobial resistance

Abstract: Along with the recent spread of multidrug-resistant bacteria, outbreaks of extended-spectrum β-lactamase (ESBL) and carbapenemase-producing bacteria present a serious challenge to clinicians. β-lactam antibiotics are the most frequently used antibacterial agents and ESBLs, and carbapenemases confer resistance not only to carbapenem antibiotics but also to penicillin and cephem antibiotics. The mechanism of β-lactam resistance involves an efflux pump, reduced permeability, altered transpeptidases, and inactivation by β-lactamases. Horizontal gene transfer is the most common mechanism associated with the spread of extended-spectrum β-lactam- and carbapenem resistance among pathogenic bacterial species. Along with the increase in antimicrobial resistance, many different types of ESBLs and carbapenemases have emerged with different enzymatic characteristics. For example, carbapenemases are represented across classes A to D of the Ambler classification system. Because bacteria harboring different types of ESBLs and carbapenemases require specific therapeutic strategies, it is essential for clinicians to understand the characteristics of infecting pathogens. In this review, we summarize the current knowledge on carbapenem resistance by ESBLs and carbapenemases, such as class A carbapenemases, class C extended-spectrum AmpC (ESAC), carbapenem-hydrolyzing class D β-lactamases (CHDLs), and class B metallo-β-lactamases, with the aim of aiding critical care clinicians in their therapeutic decision making.

Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: a meta-regression analysis

Abstract: Our recent meta-analysis indicated that vitamin C may shorten the length of ICU stay and the duration of mechanical ventilation. Here we analyze modification of the vitamin C effect on ventilation time, by the control group ventilation time (which we used as a proxy for severity of disease in the patients of each trial). We searched MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials and reference lists of relevant publications. We included controlled trials in which the administration of vitamin C was the only difference between the study groups. We did not limit our search to randomized trials and did not require placebo control. We included all doses and all durations of vitamin C administration. One author extracted study characteristics and outcomes from the trial reports and entered the data in a spreadsheet. Both authors checked the data entered against the original reports. We used meta-regression to examine whether the vitamin C effect on ventilation time depends on the duration of ventilation in the control group. We identified nine potentially eligible trials, eight of which were included in the meta-analysis. We pooled the results of the eight trials, including 685 patients in total, and found that vitamin C shortened the length of mechanical ventilation on average by 14% (P = 0.00001). However, there was significant heterogeneity in the effect of vitamin C between the trials. Heterogeneity was fully explained by the ventilation time in the untreated control group. Vitamin C was most beneficial for patients with the longest ventilation, corresponding to the most severely ill patients. In five trials including 471 patients requiring ventilation for over 10 h, a dosage of 1–6 g/day of vitamin C shortened ventilation time on average by 25% (P < 0.0001). We found strong evidence that vitamin C shortens the duration of mechanical ventilation, but the magnitude of the effect seems to depend on the duration of ventilation in the untreated control group. The level of baseline illness severity should be considered in further research. Different doses should be compared directly in future trials.

Factors influencing liberation from mechanical ventilation in coronavirus disease 2019: multicenter observational study in fifteen Italian ICUs

Abstract: A large proportion of patients with coronavirus disease 2019 (COVID-19) develop severe respiratory failure requiring admission to the intensive care unit (ICU) and about 80% of them need mechanical ventilation (MV). These patients show great complexity due to multiple organ involvement and a dynamic evolution over time; moreover, few information is available about the risk factors that may contribute to increase the time course of mechanical ventilation. The primary objective of this study is to investigate the risk factors associated with the inability to liberate COVID-19 patients from mechanical ventilation. Due to the complex evolution of the disease, we analyzed both pulmonary variables and occurrence of non-pulmonary complications during mechanical ventilation. The secondary objective of this study was the evaluation of risk factors for ICU mortality. This multicenter prospective observational study enrolled 391 patients from fifteen COVID-19 dedicated Italian ICUs which underwent invasive mechanical ventilation for COVID-19 pneumonia. Clinical and laboratory data, ventilator parameters, occurrence of organ dysfunction, and outcome were recorded. The primary outcome measure was 28 days ventilator-free days and the liberation from MV at 28 days was studied by performing a competing risks regression model on data, according to the method of Fine and Gray; the event death was considered as a competing risk. Liberation from mechanical ventilation was achieved in 53.2% of the patients (208/391). Competing risks analysis, considering death as a competing event, demonstrated a decreased sub-hazard ratio for liberation from mechanical ventilation (MV) with increasing age and SOFA score at ICU admission, low values of PaO2/FiO2 ratio during the first 5 days of MV, respiratory system compliance (CRS) lower than 40 mL/cmH2O during the first 5 days of MV, need for renal replacement therapy (RRT), late-onset ventilator-associated pneumonia (VAP), and cardiovascular complications. ICU mortality during the observation period was 36.1% (141/391). Similar results were obtained by the multivariate logistic regression analysis using mortality as a dependent variable. Age, SOFA score at ICU admission, CRS, PaO2/FiO2, renal and cardiovascular complications, and late-onset VAP were all independent risk factors for prolonged mechanical ventilation in patients with COVID-19. NCT04411459

Thromboembolic disease in COVID-19 patients: A brief narrative review

Abstract: Corona virus 2 (SARS-CoV2/ Severe Acute Respiratory Syndrome Corona Virus 2) infection has emerged as a global health crisis. Incidence of thromboembolic disease is reported to be high in SARS-CoV2 disease and is seen in a multitude of organ systems ranging from cutaneous thrombosis to pulmonary embolism, stroke or coronary thrombosis sometimes with catastrophic outcomes. Evidence points towards a key role of thromboembolism, hypercoagulability and over production of proinflammatory cytokines mimicking a “cytokine storm” which leads to multiorgan failure. This brief narrative review highlights the pathophysiology and risk factors of thromboembolic disease and provides a framework for management of anticoagulation based on the current evidence.

Monocyte distribution width enhances early sepsis detection in the emergency department beyond SIRS and qSOFA.

Abstract: The initial presentation of sepsis in the emergency department (ED) is difficult to distinguish from other acute illnesses based upon similar clinical presentations. A new blood parameter, a measurement of increased monocyte volume distribution width (MDW), may be used in combination with other clinical parameters to improve early sepsis detection. We sought to determine if MDW, when combined with other available clinical parameters at the time of ED presentation, improves the early detection of sepsis. A retrospective analysis of prospectively collected clinical data available during the initial ED encounter of 2158 adult patients who were enrolled from emergency departments of three major academic centers, of which 385 fulfilled Sepsis-2 criteria, and 243 fulfilled Sepsis-3 criteria within 12 h of admission. Sepsis probabilities were determined based on MDW values, alone or in combination with components of systemic inflammatory response syndrome (SIRS) or quick sepsis-related organ failure assessment (qSOFA) score obtained during the initial patient presentation (i.e., within 2 h of ED admission). Abnormal MDW (> 20.0) consistently increased sepsis probability, and normal MDW consistently reduced sepsis probability when used in combination with SIRS criteria (tachycardia, tachypnea, abnormal white blood count, or body temperature) or qSOFA criteria (tachypnea, altered mental status, but not hypotension). Overall, and regardless of other SIRS or qSOFA variables, MDW > 20.0 (vs. MDW ≤ 20.0) at the time of the initial ED encounter was associated with an approximately 6-fold increase in the odds of Sepsis-2, and an approximately 4-fold increase in the odds of Sepsis-3. MDW improves the early detection of sepsis during the initial ED encounter and is complementary to SIRS and qSOFA parameters that are currently used for this purpose. This study supports the incorporation of MDW with other readily available clinical parameters during the initial ED encounter for the early detection of sepsis. ClinicalTrials.gov, NCT03145428. First posted May 9, 2017. The first subjects were enrolled June 19, 2017, and the study completion date was January 26, 2018.

Early prediction of high flow nasal cannula therapy outcomes using a modified ROX index incorporating heart rate.

Abstract: The ROX index (ratio of pulse oximetry/FIO2 to respiratory rate) has been validated to predict high flow nasal cannula therapy (HFNC) outcomes in patients with pneumonia We evaluated a modified ROX index incorporating heart rate (HR) in patients initiated on HFNC for acute hypoxemic respiratory failure and as a preventative treatment following planned extubation We performed a prospective observational cohort study of 145 patients treated with HFNC ROX-HR index was defined as the ratio of ROX index over HR (beats/min), multiplied by a factor of 100 Evaluation was performed using area under the receiving operating characteristic curve (AUROC) and cutoffs assessed for prediction of HFNC failure: defined as the need for mechanical ventilation Ninety-nine (683%) and 46 (317%) patients were initiated on HFNC for acute hypoxemic respiratory failure and following a planned extubation, respectively The majority (869%) of patients had pneumonia as a primary diagnosis, and 85 (566%) patients were immunocompromised Sixty-one (421%) patients required intubation (HFNC failure) Amongst patients on HFNC for acute respiratory failure, HFNC failure was associated with a lower ROX and ROX-HR index recorded at time points between 1 and 48 h Within the first 12 h, both indices performed with the highest AUROC at 10 h as follows: 0723 (95% CI 0605–0840) and 0739 (95% CI 0626–0853) for the ROX and ROX-HR index respectively A ROX-HR index of > 680 was significantly associated with a lower risk of HFNC failure (hazard ratio 0301 (95% CI 0143–0663)) at 10 h This association was also observed at 2, 6, 18, and 24h, even with correction for potential confounding factors For HFNC initiated post-extubation, only the ROX-HR index remained significantly associated with HFNC failure at all recorded time points between 1 and 24 h A ROX-HR > 800 at 10 h was significantly associated with a lower risk of HFNC failure (hazard ratio 0176 (95% CI 0051–0604)) While validation studies are required, the ROX-HR index appears to be a promising tool for early identification of treatment failure in patients initiated on HFNC for acute hypoxemic respiratory failure or as a preventative treatment after a planned extubation

The higher the better? Defining the optimal beta-lactam target for critically ill patients to reach infection resolution and improve outcome

Abstract: Beta-lactam antibiotics are often subject to therapeutic drug monitoring, but breakpoints of target attainment are mostly based on expert opinions. Studies that show a correlation between target attainment and infection resolution are missing. This analysis investigated whether there is a difference in infection resolution based on two breakpoints of target attainment. An outcome group out of 1392 critically ill patients treated with meropenem or piperacillin-tazobactam was formed due to different selection criteria. Afterwards, three groups were created: group 1=free drug concentration (f) was MIC), group 2=100% fT > MIC 4xMIC. Parameters for infection control, renal and liver function, and estimated and observed in-hospital mortality were compared between those groups. Statistical analysis was performed with one-way analysis of variance, Tukey post hoc test, U test, and bivariate logistic regression. The outcome group consisted of 55 patients (groups 1–3, 17, 24, and 14 patients, respectively). Patients allocated to group 2 or 3 had a significantly faster reduction of the C-reactive protein in contrast to patients allocated to group 1 (p = 0.033 and p = 0.026). Patients allocated to group 3 had a worse renal function, a higher Acute Physiology and Chronic Health Evaluation (APACHE II) score, were older, and had a significantly higher in-hospital mortality compared to group 1 (p = 0.017) and group 2 (p = 0.001). The higher mortality was significantly influenced by worse liver function, higher APACHE II, and higher Sequential Organ Failure Assessment (SOFA) score and norepinephrine therapy. Achieving the target 100% fT > MIC leads to faster infection resolution in the critically ill. However, there was no benefit for patients who reached the highest target of 100% fT > 4xMIC, although the mortality rate was higher possibly due to confounding effects. In conclusion, we recommend the target 100% fT > MIC < 4xMIC for critically ill patients. NCT03985605

Neuromuscular blockade in acute respiratory distress syndrome: a systematic review and meta-analysis of randomized controlled trials

Abstract: Neuromuscular blocking agent (NMBA) has been proposed by medical guidelines for early severe acute respiratory distress syndrome (ARDS) because of its survival benefits. However, new studies have provided evidence contradicting these results. A search was performed of the Pubmed, Scopus, Clinicaltrials.gov, and Virtual Health Library databases for randomized controlled trials (RCT) evaluating 28-day mortality in ARDS patients treated with NMBA within 48 h. An English language restriction was applied. Relevant data were extracted and pooled into risk ratios (RR), mean differences (MD), and corresponding 95% confidence intervals (CI) using random-effect model. Sensitivity and meta-regression analysis were performed. From 2675 studies, we included five RCTs in the analysis, for a total of 1461 patients with a mean PaO2/FIO2 of 104 ± 35 mmHg. The cisatracurium group had the same risk of death at 28 days (RR, 0.90; 95% CI, 0.78–1.03; I2 = 50%, p = 0.12) and 90 days (RR, 0.81; 95% CI, 0.62–1.06; I2 = 56%, p = 0.06) as the control group (no cisatracurium). The secondary outcomes of mechanical ventilation duration and ventilator-free days were not different between the two groups. Cisatracurium had a significantly lower risk of barotrauma than the control group with no difference in intensive care unit (ICU)–induced weakness. The PaO2/FIO2 ratio was higher in the cisatracurium group but not until 48 h. Meta-regression analysis of the baseline PaO2/FIO2 ratio, positive end-expiratory pressure (PEEP) revealed no heterogeneity. Subgroup analysis excluding the trial using high PEEP and light sedation strategy yielded an improvement in all mortality outcomes. NMBA improves oxygenation only after 48 h in moderate, severe ARDS patients and has a lower barotrauma risk without affecting ICU weakness. However, NMBA does not reduce ventilator-free days, duration of mechanical ventilation or, most importantly, the mortality risk regardless of the severity of ARDS.

Prevalence and prognostic value of elevated troponins in patients hospitalised for coronavirus disease 2019: a systematic review and meta-analysis.

Abstract: The clinical significance of cardiac troponin measurement in patients hospitalised for coronavirus disease 2019 (covid-19) is uncertain. We investigated the prevalence of elevated troponins in these patients and its prognostic value for predicting mortality. Studies were identified by searching electronic databases and preprint servers. We included studies of hospitalised covid-19 patients that reported the frequency of troponin elevations above the upper reference limit and/or the association between troponins and mortality. Meta-analyses were performed using random-effects models. Fifty-one studies were included. Elevated troponins were found in 20.8% (95% confidence interval [CI] 16.8–25.0 %) of patients who received troponin test on hospital admission. Elevated troponins on admission were associated with a higher risk of subsequent death (risk ratio 2.68, 95% CI 2.08–3.46) after adjusting for confounders in multivariable analysis. The pooled sensitivity of elevated admission troponins for predicting death was 0.60 (95% CI 0.54–0.65), and the specificity was 0.83 (0.77–0.88). The post-test probability of death was about 42% for patients with elevated admission troponins and was about 9% for those with non-elevated troponins on admission. There was significant heterogeneity in the analyses, and many included studies were at risk of bias due to the lack of systematic troponin measurement and inadequate follow-up. Elevated troponins were relatively common in patients hospitalised for covid-19. Troponin measurement on admission might help in risk stratification, especially in identifying patients at high risk of death when troponin levels are elevated. High-quality prospective studies are needed to validate these findings. PROSPERO CRD42020176747

Efficacy of probiotics in the prevention of VAP in critically ill ICU patients: an updated systematic review and meta-analysis of randomized control trials.

Abstract: Ventilator-associated pneumonia (VAP) is reported as the second most common nosocomial infection among critically ill patients with the incidence ranging from 2 to 16 episodes per 1000 ventilator days. The use of probiotics has been shown to have a promising effect in many RCTs. Our systematic review and meta-analysis were thus planned to determine the effect of probiotic use in critically ill ventilated adult patients on the incidence of VAP, length of hospital stay, length of ICU stay, duration of mechanical ventilation, the incidence of diarrhea, and the incidence of oropharyngeal colonization and in-hospital mortality. Systematic search of various databases (such as Embase, Cochrane, and Pubmed), published journals, clinical trials, and abstracts of the various major conferences were made to obtain the RCTs which compare probiotics with placebo for VAP prevention. The results were expressed as risk ratios or mean differences. Data synthesis was done using statistical software - Review Manager (RevMan) Version 5.4 (The Cochrane Collaboration, 2020). Nine studies met our inclusion criterion and were included in the meta-analysis. The incidence of VAP (risk ratio: 0.70, CI 0.56, 0.88; P = 0.002; I2 = 37%), duration of mechanical ventilation (mean difference −3.75, CI −6.93, −0.58; P 0.02; I2 = 96%), length of ICU stay (mean difference −4.20, CI −6.73, −1.66; P = 0.001; I2 = 84%) and in-hospital mortality (OR 0.73, CI 0.54, 0.98; P = 0.04; I2 = 0%) in the probiotic group was significantly lower than that in the control group. Probiotic administration was not associated with a statistically significant reduction in length of hospital stay (MD −1.94, CI −7.17, 3.28; P = 0.47; I2 = 88%), incidence of oro-pharyngeal colonization (OR 0.59, CI 0.33, 1.04; P = 0.07; I2 = 69%), and incidence of diarrhea (OR 0.59, CI 0.34, 1.03; P = 0.06; I2 = 38%). Our meta-analysis shows that probiotic administration has a promising role in lowering the incidence of VAP, the duration of mechanical ventilation, length of ICU stay, and in-hospital mortality.

Patients suffering from psychological impairments following critical illness are in need of information.

Abstract: Because critical illness survivors frequently experience several long-term psychological impairments altering quality of life after ICU, there is a trend towards increasing follow-up care, mainly via ICU follow-up clinics. Despite these and other initiatives, understanding of patient’s post-ICU needs to help them cope with their problems and subsequently improve quality of life is largely lacking. Our aim was therefore to assess the needs, expectations and wishes in ICU survivors to receive information with the purpose to help them better grasp ICU treatment. In addition, we assessed the perceived burden of psychological trauma after ICU treatment and the health-related quality of life (HRQoL) up to 2.5 years after ICU discharge. In a multicentre, retrospective cross-sectional cohort study, the needs and preferred intervention methods were assessed using a self-composed inventory in adult mechanically ventilated ICU survivors (n = 43). Additionally, the Impact of Event Scale Revised, the Beck Depression Inventory, the EuroQol-5D-5L, and the Short-Form 12 were used to assess psychological burden and HRQoL. A substantial proportion of all ICU survivors (59%, 95% CI 44% to 74%) suffered from psychological impairments after ICU treatment. Seventy-five percent of these patients expressed a wish to receive information, but only 36% desired to receive this information using a commonly used information brochure. In contrast, 71% of these patients had a wish to receive information using a video film/VR. Furthermore, only 33% of these patients was satisfied with the information provided by their treating hospital. Patients with psychological PICS reported a worse HRQoL as compared to a normative Dutch sample (P < 0.001) and as compared to patients without psychological PICS (P < 0.01). In a Dutch cohort of critical illness survivors, a substantial part of ICU survivors suffer from psychological impairments, such as PTSD and depression, which was associated with a worse HRQoL. These patients are in need of information, have no desire using an information brochure, but are willing to receive information using a video film/virtual reality module. These results support the exploration of such an intervention.

Development of a nomogram to predict 30-day mortality of patients with sepsis-associated encephalopathy: a retrospective cohort study

Abstract: Sepsis-associated encephalopathy (SAE) is related to increased short-term mortality in patients with sepsis. We aim to establish a user-friendly nomogram for individual prediction of 30-day risk of mortality in patients with SAE. Data were retrospectively retrieved from the Medical Information Mart for Intensive Care (MIMIC III) open source clinical database. SAE was defined by Glasgow Coma Score (GCS) < 15 or delirium at the presence of sepsis. Prediction model with a nomogram was constructed in the training set by logistic regression analysis and then undergone internal validation and sensitivity analysis. SAE accounted for about 50% in patients with sepsis and was independently associated with the 30-day mortality of sepsis. Variables eligible for the nomogram included patient’s age and clinical parameters on the first day of ICU admission including the GCS score, lactate, bilirubin, red blood cell distribution width (RDW), mean value of respiratory rate and temperature, and the use of vasopressor. Compared with Sequential Organ Failure Assessment (SOFA) and Logistic Organ Dysfunction System (LODS), the nomogram exhibited better discrimination with an area under the receiver operating characteristic curve (AUROC) of 0.763 (95%CI 0.736–0.791, p < 0.001) and 0.753 (95%CI 0.713–0.794, p < 0.001) in the training and validation sets, respectively. The calibration plot revealed an adequate fit of the nomogram for predicting the risk of 30-day mortality in both sets. Regarding to clinical usefulness, the DCA of the nomogram exhibited greater net benefit than SOFA and LODS in both of the training and validation sets. Besides, the nomogram exhibited acceptable discrimination, calibration, and clinical usefulness in sensitivity analysis. SAE is related to increased 30-day mortality of patients with sepsis. The nomogram presents excellent performance in predicting 30-day risk of mortality in SAE patients, which can be used to evaluate the prognosis of patients with SAE and may be more beneficial once specific treatments towards SAE are developed.

Management of life-threatening hemoptysis.

Abstract: It is estimated that 5–14% of patients presenting with hemoptysis will have life-threatening hemoptysis, with a reported mortality rate between 9 and 38%. This manuscript provides a comprehensive literature review on life-threatening hemoptysis, including the etiology and mechanisms, initial stabilization, and management of patients. There is no consensus on the optimal diagnostic approach to life-threatening hemoptysis, so we present a practical approach to utilizing chest radiography, computed tomography, and bronchoscopy, alone or in combination, to localize the bleeding site depending on patient stability. The role of angiography and embolization as well as bronchoscopic and surgical techniques for the management of life-threatening hemoptysis is reviewed. Through case presentation and flow diagram, an overview is provided on how to systematically evaluate and treat the bronchial arteries, which are responsible for hemoptysis in 90% of cases. Treatment options for recurrent hemoptysis and definitive management are discussed, highlighting the role of bronchial artery embolization for recurrent hemoptysis.

Neuromuscular blockade management in the critically Ill patient

Abstract: Neuromuscular blocking agents (NMBAs) can be an effective modality to address challenges that arise daily in the intensive care unit (ICU). These medications are often used to optimize mechanical ventilation, facilitate endotracheal intubation, stop overt shivering during therapeutic hypothermia following cardiac arrest, and may have a role in the management of life-threatening conditions such as elevated intracranial pressure and status asthmaticus (when deep sedation fails or is not tolerated). However, current NMBA use has decreased during the last decade due to concerns of potential adverse effects such as venous thrombosis, patient awareness during paralysis, development of critical illness myopathy, autonomic interactions, and even residual paralysis following cessation of NMBA use. It is therefore essential for clinicians to be familiar with evidence-based practices regarding appropriate NMBA use in order to select appropriate indications for their use and avoid complications. We believe that selecting the right NMBA, administering concomitant sedation and analgesic therapy, and using appropriate monitoring techniques mitigate these risks for critically ill patients. Therefore, we review the indications of NMBA use in the critical care setting and discuss the most appropriate use of NMBAs in the intensive care setting based on their structure, mechanism of action, side effects, and recognized clinical indications. Lastly, we highlight the available pharmacologic antagonists, strategies for sedation, newer neuromuscular monitoring techniques, and potential complications related to the use of NMBAs in the ICU setting.

Linkage of alterations in systemic iron homeostasis to patients' outcome in sepsis: a prospective study.

Abstract: Sepsis, a dysregulated host response following infection, is associated with massive immune activation and high mortality rates. There is still a need to define further risk factors and laboratory parameters predicting the clinical course. Iron metabolism is regulated by both, the body’s iron status and the immune response. Iron itself is required for erythropoiesis but also for many cellular and metabolic functions. Moreover, iron availability is a critical determinant in infections because it is an essential nutrient for most microbes but also impacts on immune function and intravascular oxidative stress. Herein, we used a prospective study design to investigate the putative impact of serum iron parameters on the outcome of sepsis. Serum markers of iron metabolism were measured in a prospective cohort of 61 patients (37 males, 24 females) with sepsis defined by Sepsis-3 criteria in a medical intensive care unit (ICU) and compared between survivors and non-survivors. Regulation of iron parameters in patients stratified by focus of infection and co-medication as well as association of the markers with sepsis severity scores and survival were investigated with linear and logistic regression corrected for sex and age effects. Positive correlations of increased serum iron and ferritin concentrations upon ICU admission with the severity of organ failure (SOFA score) and with mortality were observed. Moreover, high TF-Sat, elevated ferritin and serum iron levels and low transferrin concentrations were associated with reduced survival. A logistic regression model consisting of SOFA and transferrin saturation (SOFA–TF-Sat) had the best predictive power for survival in septic ICU patients. Of note, administration of blood transfusions prior to ICU admission resulted in increased TF-Sat and reduced survival of septic patients. Our study could show an important impact of serum iron parameters on the outcome of sepsis. Furthermore, we identified transferrin saturation as a stand-alone predictor of sepsis survival and as a parameter of iron metabolism which may in a combined model improve the prediction power of the SOFA score. The study was carried out in accordance with the recommendations of the Declaration of Helsinki on biomedical research. The study was approved by the institutional ethics review board of the Medical University Innsbruck (study AN2013-0006 ).

Association between visitation restriction during the COVID-19 pandemic and delirium incidence among emergency admission patients: a single-center retrospective observational cohort study in Japan

Abstract: This study aimed to identify the association between total visitation restriction because of the coronavirus 2019 (COVID-19) pandemic and the incidence of delirium for emergency inpatients. This was a single-center, retrospective, observational cohort study conducted at a tertiary critical care center in urban Kyoto, Japan. Adult emergency patients hospitalized between January 1, 2019, and June 30, 2020, were recruited. In response to the COVID-19 pandemic, the authors’ hospital began restricted visitation on March 28, 2020. This study defined before visitation restriction as January 1, 2019, through March 31, 2020, and after visitation restriction as April 1, 2020, through June 30, 2020. We did not restrict emergency services, and there were no changes in the hospital’s routine, except for visitation restrictions. The primary outcome was the incidence of delirium. The adjusted odds ratio (AOR) with 95% confidence interval (CI) for delirium incidence was calculated to compare the before and after visitation restriction periods, and the logistic model was used to adjust for seven variables: age, sex, ward type on admission, primary diagnosis, ventilator management, general anesthesia surgery, and dementia. Study participants were 6264 patients, median age 74 years (56–83), and 3303 men (52.7%). The total delirium incidence in entire research period was 2.5% (158 of 6264 patients), comprising 1.8% (95/5251) before visitation restriction and 6.2% (63/1013) after visitation restriction. The AOR for delirium incidence was 3.79 (95% CI, 2.70–5.31) after visitation restriction versus before visitation restriction. Subgroup analysis showed no apparent interaction for delirium incidence. Visitation restriction was associated with an increased incidence of delirium in emergency inpatients.

Use of glucocorticoids in patients with acute respiratory distress syndrome: a meta-analysis and trial sequential analysis

Abstract: Acute respiratory distress syndrome (ARDS) is a common and disabling disease with high rates of mortality and morbidity. The role of steroids in treating ARDS remains controversial. We aim to examine the evidence behind using glucocorticoids in the management of ARDS from the available studies. We performed a literature review of major electronic databases for randomized controlled trials (RCTs) comparing glucocorticoids versus placebo in treating patients with ARDS. Our primary outcome was hospital mortality. Other outcomes included ICU mortality, number of ventilator-free days at day 28, incidence of nosocomial infections, and hyperglycemia. We performed a meta-analysis using a random effects model to calculate risk ratios (RR) and mean difference (MD) with their corresponding 95% confidence intervals (CI). A subsequent trial sequential analysis was performed to examine the strength of evidence and to guard against statistical type I and type II errors for our results. Eight RCTs were included in the final analysis totaling of 1091 patients, with a mean age of 57 ± 16, and 56.2% were male. In our pooled analysis, use of glucocorticoids was associated with a significant reduction in hospital mortality (RR 0.79; 95% CI 0.64–0.98; P = 0.03) and ICU mortality (RR 0.64; 95% CI 0.42–0.97; P = 0.04). Furthermore, glucocorticoid use was associated with an increased number of ventilator-free days at day 28 (MD 4.06 days; 95% CI 2.66–5.45; P < 0.01). Regarding adverse events, glucocorticoids use was not associated with an increased risk for nosocomial infections (RR 0.82; 95% CI 0.68–1.00; P = 0.05); however, it was associated with an increased risk of hyperglycemia (RR 1.11; 95% CI 1.01–1.24; P = 0.04). In our trial sequential analysis, the required diversity-adjusted information size (sample size = 2692 patients) was not reached, and the evidence was insufficient from the available RCTs. Among patients with ARDS, use of glucocorticoids is associated with a significant reduction in mortality and duration of mechanical ventilation, without increased risk of hospital-acquired infections. However, based on a trial sequential analysis, these findings may be secondary to a false-positive (type I) error. Further studies are needed for a firm conclusion with guarding against possible statistical errors.

Dexmedetomidine improved renal function in patients with severe sepsis: an exploratory analysis of a randomized controlled trial.

Abstract: Dexmedetomidine has been reported to improve organ dysfunction in critically ill patients. In a recent randomized controlled trial (Dexmedetomidine for Sepsis in Intensive Care Unit (ICU) Randomized Evolution [DESIRE]), we demonstrated that dexmedetomidine was associated with reduced mortality risk among patients with severe sepsis. We performed this exploratory sub-analysis to examine the mechanism underlying improved survival in patients sedated with dexmedetomidine. The DESIRE trial compared a sedation strategy with and without dexmedetomidine among 201 mechanically ventilated adult patients with sepsis across eight ICUs in Japan. In the present study, we included 104 patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of ≥ 23 (54 in the dexmedetomidine [DEX] group and 50 in the non-dexmedetomidine [non-DEX] group). Initially, we compared the changes in the sequential organ failure assessment (SOFA) scores from the baseline within 6 days after randomization between groups. Subsequently, we evaluated the variables comprising the organ component of the SOFA score that showed relevant improvement in the initial comparison. The mean patient age was 71.0 ± 14.1 years. There was no difference in the median APACHE II score between the two groups (29 [interquartile range (IQR), 25–31] vs. 30 [IQR, 25–33]; p = 0.35). The median SOFA score at the baseline was lower in the DEX group (9 [IQR, 7–11] vs. 11 [IQR, 9–13]; p = 0.01). While the renal SOFA subscore at the baseline was similar for both groups, it significantly decreased in the DEX group on day 4 (p = 0.02). During the first 6 days, the urinary output was not significantly different (p = 0.09), but serum creatinine levels were significantly lower (p = 0.04) in the DEX group. The 28-day and in-hospital mortality rates were significantly lower in the DEX group (22% vs. 42%; p = 0.03, 28% vs. 52%; p = 0.01, respectively). A sedation strategy with dexmedetomidine is associated with improved renal function and decrease mortality rates among patients with severe sepsis. This trial was registered on ClinicalTrials.gov (NCT01760967) on January 1, 2013.

Prolonged versus intermittent β-lactam antibiotics intravenous infusion strategy in sepsis or septic shock patients: a systematic review with meta-analysis and trial sequential analysis of randomized trials

Abstract: The prolonged β-lactam infusion strategy has emerged as the standard treatment for sepsis or septic shock despite its unknown efficacy. This study aimed to assess the efficacy of prolonged versus intermittent β-lactam antibiotics infusion on outcomes in sepsis or septic shock patients by conducting a systematic review and meta-analysis. A thorough search was conducted on MEDLINE, the Cochrane Central Register of Controlled Trials, and the Igaku Chuo Zasshi databases. Randomized controlled trials (RCTs) comparing mortality between prolonged and intermittent infusion in adult patients with sepsis or septic shock were included. The primary outcome was hospital mortality. The secondary outcomes were the attainment of the target plasma concentration, clinical cure, adverse events, and occurrence of antibiotic-resistant bacteria. We performed a subgroup analysis stratified according to the year of publication before or after 2015 and a trial sequential analysis (TSA). The Der Simonian–Laird random-effects models were subsequently used to report the pooled risk ratios (RR) with confidence intervals (CI). We identified 2869 studies from the 3 databases, and 13 studies were included in the meta-analysis. Hospital mortality did not decrease (RR 0.69 [95%CI 0.47–1.02]) in the prolonged infusion group. The attainment of the target plasma concentration and clinical cure significantly improved (RR 0.40 [95%CI 0.21–0.75] and RR 0.84 [95%CI 0.73–0.97], respectively) in the prolonged infusion group. There were, however, no significant differences in the adverse events and the occurrence of antibiotic-resistant bacteria between the groups (RR 1.01 (95%CI 0.95–1.06) and RR 0.53 [95%CI 0.10–2.83], respectively). For the subgroup analysis, a significant improvement in hospital mortality or clinical cure was reported in studies published in or after 2015 (RR 0.66 [95%CI 0.44–0.98] and RR 0.67 [95%CI 0.50–0.90], respectively). The results of the TSA indicated an insufficient number of studies for a definitive analysis. The prolonged infusion of β-lactam antibiotics significantly improved upon attaining the target plasma concentration and clinical cure without increasing the adverse event or the occurrence of antibiotic-resistant bacteria. Prolonged infusion could not improve hospital mortality although an improvement was shown for studies published in or after 2015. Further studies are warranted as suggested by our TSA results.

Variables predicting weaning outcome in prolonged mechanically ventilated tracheotomized patients: a retrospective study

Abstract: Several studies have assessed predictors of weaning and extubation outcome in short-term mechanically ventilated patients, but there are only few studies on predictors of weaning from prolonged mechanical ventilation. Retrospective, single-center, observational study at a specialized national weaning center in Germany. Patients’ medical records were reviewed to obtain data on demographics, comorbidities, respiratory indices, and the result of a prospectively documented, standardized spontaneous breathing trial (SBT) upon admission to the weaning center. Respiratory indices assessed were the ventilatory ratio (VR) and parameters derived from calculated mechanical power (MP). Predictors associated with failure of prolonged weaning and failure of the SBT were assessed using a binary logistic regression model. A total of 263 prolonged mechanically ventilated, tracheotomized patients, treated over a 5-year period were analyzed. After 3 weeks of mechanical ventilation, patients with unsuccessful weaning failed a SBT more frequently and showed significantly increased values for inspiratory positive airway pressure, driving pressure, VR, absolute MP, and MP normalized to predicted body weight and dynamic lung-thorax compliance (LTC-MP). In the logistic regression analyses, variables independently correlated with weaning failure were female gender (adjusted odds ratio 0.532 [95% CI 0.291–0.973]; p = 0.040), obesity (body mass index ≥ 30 kg/m2) (2.595 [1.210–5.562]; p = 0.014), COPD (3.209 [1.563–6.589]; p = 0.002), LTC-MP (3.470 [1.067–11.284]; p = 0.039), PaCO2 on mechanical ventilation (1.101 [95% CI 1.034–1.173]; p = 0.003), and failure of the SBT (4.702 [2.250–9.825]; p < 0.001). In addition, female gender (0.401 [0.216–0.745]; p = 0.004), LTC-MP (3.017 [1.027–8.862]; p = 0.046), and PaCO2 on mechanical ventilation (1.157 [1.083–1.235]; p < 0.001) were independent risk factors for an unsuccessful SBT. In the present study, the derived predictors of weaning point to a crucial role of the workload imposed on respiratory muscles during spontaneous breathing. Mechanical power normalized to lung-thorax compliance was independently correlated with weaning outcome and may identify patients at high risk for weaning failure.

Epidemiology of sepsis and septic shock in intensive care units between sepsis-2 and sepsis-3 populations: sepsis prognostication in intensive care unit and emergency room (SPICE-ICU)

Abstract: Diagnosing sepsis remains difficult because it is not a single disease but a syndrome with various pathogen- and host factor-associated symptoms. Sepsis-3 was established to improve risk stratification among patients with infection based on organ failures, but it has been still controversial compared with previous definitions. Therefore, we aimed to describe characteristics of patients who met sepsis-2 (severe sepsis) and sepsis-3 definitions. This was a multicenter, prospective cohort study conducted by 22 intensive care units (ICUs) in Japan. Adult patients (≥ 16 years) with newly suspected infection from December 2017 to May 2018 were included. Those without infection at final diagnosis were excluded. Patient’s characteristics and outcomes were described according to whether they met each definition or not. In total, 618 patients with suspected infection were admitted to 22 ICUs during the study, of whom 530 (85.8%) met the sepsis-2 definition and 569 (92.1%) met the sepsis-3 definition. The two groups comprised different individuals, and 501 (81.1%) patients met both definitions. In-hospital mortality of study population was 19.1%. In-hospital mortality among patients with sepsis-2 and sepsis-3 patients was comparable (21.7% and 19.8%, respectively). Patients exclusively identified with sepsis-2 or sepsis-3 had a lower mortality (17.2% vs. 4.4%, respectively). No patients died if they did not meet any definitions. Patients who met sepsis-3 shock definition had higher in-hospital mortality than those who met sepsis-2 shock definition. Most patients with infection admitted to ICU meet sepsis-2 and sepsis-3 criteria. However, in-hospital mortality did not occur if patients did not meet any criteria. Better criteria might be developed by better selection and combination of elements in both definitions. UMIN000027452

Oxygen administration for postoperative surgical patients: a narrative review

Abstract: Most postoperative surgical patients routinely receive supplemental oxygen therapy to prevent the potential development of hypoxemia due to incomplete lung re-expansion, reduced chest wall, and diaphragmatic activity caused by surgical site pain, consequences of hemodynamic impairment, and residual effects of anesthetic drugs (most notably residual neuromuscular blockade), which may result in atelectasis, ventilation-perfusion mismatch, alveolar hypoventilation, and impaired upper airway patency. Additionally, the World Health Organization guidelines for reducing surgical site infection have recommended the perioperative administration of high-dose oxygen, including during the immediate postoperative period. However, supplemental oxygen and hyperoxemia also have harmful effects on the respiratory and cardiovascular systems, with several clinical studies having reported an association between high perioperative oxygen administration and worse clinical outcomes. Recently, the increased availability of new and short-acting anesthetic drugs, comprehensive pharmacological knowledge, postoperative multimodal analgesia, and new minimally invasive surgery options could result in lower incidences of postoperative hypoxemia. Moreover, recommendations promoting high oxygen administration to prevent surgical site infections have been challenged, considering the lack of scientific investigations, and have not been widely accepted. Given the potential harmful effects of hyperoxemia, routine postoperative oxygen administration might not be recommended. Recent clinical studies have indicated that a conservative approach to oxygen therapy, where oxygen administration is titrated to achieve slightly lower oxygen levels than usual, could be safely implemented and decrease acutely ill patients' susceptibility to hyperoxemia. Based on current evidence, appropriate monitoring, including peripheral oxygen saturation, and oxygen titration should be required during postoperative oxygen administration to avoid both hypoxemia and hyperoxemia. Future trials should therefore focus on determining the optimal oxygen target during postoperative care.

Efficacy and safety of tranexamic acid administration in traumatic brain injury patients: a systematic review and meta-analysis.

Abstract: The exacerbation of intracranial bleeding is critical in traumatic brain injury (TBI) patients. Tranexamic acid (TXA) has been used to improve outcomes in TBI patient. However, the effectiveness of TXA treatment remains unclear. This study aimed to assess the effect of administration of TXA on clinical outcomes in patients with TBI by systematically reviewing the literature and synthesizing evidence of randomized controlled trials (RCTs). MEDLINE, the Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi (ICHUSHI) Web were searched. Selection criteria included randomized controlled trials with clinical outcomes of adult TBI patients administered TXA or placebo within 24 h after admission. Two investigators independently screened citations and conducted data extraction. The primary “critical” outcome was all-cause mortality. The secondary “important” outcomes were good neurological outcome rates, enlargement of bleeding, incidence of ischemia, and hemorrhagic intracranial complications. Random effect estimators with weights calculated by the inverse variance method were used to report risk ratios (RRs). A total of 640 records were screened. Seven studies were included for quantitative analysis. Of 10,044 patients from seven of the included studies, 5076 were randomly assigned to the TXA treatment group, and 4968 were assigned to placebo. In the TXA treatment group, 914 patients (18.0%) died, while 961 patients (19.3%) died in the placebo group. There was no significant difference between groups (RR, 0.93; 95% confidence interval, 0.86–1.01). No significant differences between the groups in other important outcomes were also observed. TXA treatment demonstrated a tendency to reduce head trauma-related deaths in the TBI population, with no significant incidence of thromboembolic events. TXA treatment may therefore be suggested in the initial TBI care.

Association between low pH and unfavorable neurological outcome among out-of-hospital cardiac arrest patients treated by extracorporeal CPR: a prospective observational cohort study in Japan

Abstract: We aimed to identify the association of pH value in blood gas assessment with neurological outcome among out-of-hospital cardiac arrest (OHCA) patients treated by extracorporeal cardiopulmonary resuscitation (ECPR). We retrospectively analyzed the database of a multicenter prospective observational study on OHCA patients in Osaka prefecture, Japan (CRITICAL study), from July 1, 2012 to December 31, 2016. We included adult OHCA patients treated by ECPR. Patients with OHCA from external causes such as trauma were excluded. We conducted logistic regression analysis to identify the odds ratio (OR) and 95% confidence interval (CI) of the pH value for 1 month favorable neurological outcome adjusted for potential confounders including sex, age, witnessed by bystander, CPR by bystander, pre-hospital initial cardiac rhythm, and cardiac rhythm on hospital arrival. Among the 9822 patients in the database, 260 patients were finally included in the analysis. The three groups were Tertile 1: pH ≥ 7.030, Tertile 2: pH 6.875–7.029, and Tertile 3: pH < 6.875. The adjusted OR of Tertiles 2 and 3 compared with Tertile 1 for 1 month favorable neurological outcome were 0.26 (95% CI 0.10–0.63) and 0.24 (95% CI 0.09–0.61), respectively. This multi-institutional observational study showed that low pH value (< 7.03) before the implementation of ECPR was associated with 1 month unfavorable neurological outcome among OHCA patients treated with ECPR. It may be helpful to consider the candidate for ECPR.

Low-chloride- versus high-chloride-containing hypertonic solution for the treatment of subarachnoid hemorrhage–related complications: The ACETatE (A low ChloriE hyperTonic solution for brain Edema) randomized trial

Abstract: Recent reports have demonstrated that among patients with subarachnoid hemorrhage (SAH) treated with hypertonic NaCl, resultant hyperchloremia has been associated with the development of acute kidney injury (AKI). We report a trial comparing the effect of two hypertonic solutions with different chloride contents on the resultant serum chloride concentrations in SAH patients, with a primary outcome aimed at limiting chloride elevation. A low ChloridE hyperTonic solution for brain Edema (ACETatE) trial is a single-center, double-blinded, double-dummy, randomized pilot trial comparing bolus infusions of 23.4% NaCl and 16.4% NaCl/Na-acetate for the treatment of cerebral edema in patients with SAH. Randomization occurred when patients developed hyperchloremia (serum Cl− ≥ 109 mmol/L) and required hyperosmolar treatment. We enrolled 59 patients, of which 32 developed hyperchloremia and required hyperosmolar treatment. 15 patients were randomized to the 23.4% NaCl group, and 17 patients were randomized to the 16.4% NaCl/Na-acetate group. Although serum chloride levels increased similarly in both groups, the NaCl/Acetate group showed a significantly lower Cl− load at the end of the study period (978mEq vs. 2,464mEq, p < 0.01). Secondary outcome analysis revealed a reduced rate of AKI in the Na-acetate group (53.3% in the NaCl group vs. 11.8% in the Na-acetate group, p = 0.01). Both solutions had similar effects on ICP reduction, but NaCl/Acetate treatment had a more prominent effect on immediate post-infusion Na+ concentrations (increase of 2.2 ± 2.8 vs. 1.4 ± 2.6, (p < 0.01)). Proximal tubule renal biomarkers differed in concentration between the two groups. Our pilot trial showed the feasibility and safety of replacing 23.4% NaCl infusions with 16.4% NaCl/Na-acetate infusions to treat cerebral edema in patients with SAH. The degree of hyperchloremia was similar in the two groups. 16.4% NaCl/Na-acetate infusions led to lower Cl− load and AKI rates than 23.4% NaCl infusions. Further multi-center studies are needed to corroborate these results. clinicaltrials.gov # NCT03204955 , registered on 6/28/2017

Perspective on fibrinolytic therapy in COVID-19: the potential of inhalation therapy against suppressed-fibrinolytic-type DIC

Abstract: A high rate of thrombotic complications, such as pulmonary embolism, has been linked to mortality in COVID-19, and appropriate treatment of thrombosis is important for lifesaving. Although heparin is frequently used to treat thrombotic pathology in COVID-19, pulmonary embolism is still seen in severe cases. Although systemic fibrinolytic therapy is a focus of attention because a thrombotic pathology is the cause of death in severe COVID-19, it should be kept in mind that fibrinolytic therapy might be harmful at advanced stage of COVID-19 where the status of disseminated intravascular coagulation (DIC) has been transmitted from suppressed-fibrinolytic to enhanced-fibrinolytic in disease progression of COVID-19. In this respect, inhalation therapy with fibrinolytic substances might be a safe and promising treatment.

Epidemiology and outcomes of sepsis among hospitalizations with systemic lupus erythematosus admitted to the ICU: a population-based cohort study.

Abstract: Sepsis is the most common cause of premature death among patients with systemic lupus erythematosus (SLE) aged ≤ 50 years in the United States, and infection is the most common cause of admission to the ICU among SLE patients. However, there are no population-level data on the patterns of the demand for critical care services among hospitalized septic patients with SLE or the outcomes of those admitted to the ICU. We performed a retrospective cohort study, using the Texas Inpatient Public Use Data File, to identify SLE hospitalizations aged ≥ 18 years and the subgroups with sepsis and ICU admission during 2009–2014. The patterns of ICU admission among septic hospitalizations were examined. Logistic regression modeling was used to identify predictors of short-term mortality (defined as hospital death or discharge to hospice) among ICU admissions with sepsis and to estimate the risk-adjusted short-term mortality among ICU admissions with and without sepsis. Among 94,338 SLE hospitalizations, 17,037 (18.1%) had sepsis and 9409 (55.2%) of the latter were admitted to the ICU. Sepsis accounted for 51.5% of the growth in volume of ICU admissions among SLE hospitalizations during the study period. Among ICU admissions with sepsis, 25.3% were aged ≥ 65 years, 88.6% were female, and 64.4% were non-white minorities. The odds of short-term mortality among septic ICU admissions were increased among those lacking health insurance (adjusted odds ratio 1.40 [95% confidence interval 1.07–1.84]), while being unaffected by gender and race/ethnicity, and remaining unchanged over the study period. On adjusted analyses among ICU admissions, the short-term mortality among those with and without sepsis was 13% (95% CI 12.6–13.3) and 2.7% (95% CI 2.6–2.8), respectively. Sepsis was associated with 63.6% of all short-term mortality events. Sepsis is a major, incremental driver of the demand for critical care services among SLE hospitalizations. Despite its relatively low mortality, sepsis was associated with most of the short-term deaths among ICU patients with SLE.

Biological effects of the oxygen molecule in critically ill patients.

Abstract: The medical use of oxygen has been widely and frequently proposed for patients, especially those under critical care; however, its benefit and drawbacks remain controversial for certain conditions. The induction of oxygen therapy is commonly considered for either treating or preventing hypoxia. Therefore, the concept of different types of hypoxia should be understood, particularly in terms of their mechanism, as the effect of oxygen therapy principally varies by the physiological characteristics of hypoxia. Oxygen molecules must be constantly delivered to all cells throughout the human body and utilized effectively in the process of mitochondrial oxidative phosphorylation, which is necessary for generating energy through the formation of adenosine triphosphate. If the oxygen availability at the cellular level is inadequate for sustaining the metabolism, the condition of hypoxia which is characterized as heterogeneity in tissue oxygen tension may develop, which is called dysoxia, a more physiological concept that is related to hypoxia. In such hypoxic patients, repetitive measurements of the lactate level in blood are generally recommended in order to select the adequate therapeutic strategy targeting a reduction in lactate production. Excessive oxygen, however, may actually induce a hyperoxic condition which thus can lead to harmful oxidative stress by increasing the production of reactive oxygen species, possibly resulting in cellular dysfunction or death. In contrast, the human body has several oxygen-sensing mechanisms for preventing both hypoxia and hyperoxia that are employed to ensure a proper balance between the oxygen supply and demand and prevent organs and cells from suffering hyperoxia-induced oxidative stress. Thus, while the concept of hyperoxia is known to have possible adverse effects on the lung, the heart, the brain, or other organs in various pathological conditions of critically ill patients, and no obvious evidence has yet been proposed to totally support liberal oxygen supplementation in any subset of critically ill patients, relatively conservative oxygen therapy with cautious monitoring appears to be safe and may improve the outcome by preventing harmful oxidative stress resulting from excessive oxygen administration. Given the biological effects of oxygen molecules, although the optimal target levels remain controversial, unnecessary oxygen administration should be avoided, and exposure to hyperoxemia should be minimized in critically ill patients.