Search

BACKGROUND: Quantitative analysis of ventricular cerebrospinal fluid (vCSF) proteins following acute brain injury (ABI) may help identify pathophysiological pathways and potential biomarkers that can predict unfavorable outcome. METHODS: In this prospective proteomic analysis study, consecutive patients with severe ABI expected to require intraventricular catheterization for intracranial pressure (ICP) monitoring for at least 5 days and patients without ABI admitted for elective clipping of an unruptured cerebral aneurysm were included. vCSF samples were collected within the first 24 h after ABI and ventriculostomy insertion and then every 24 h for 5 days. In patients without ABI, a single vCSF sample was collected at the time of elective clipping. Data-independent acquisition and sequential window acquisition of all theoretical spectra (SWATH) mass spectrometry were used to compare differences in protein expression in patients with ABI and patients without ABI and in patients with traumatic and nontraumaticABI. Differences in protein expression according to different ICP values, intensive care unit outcome, subarachnoid hemorrhage (SAH) versus traumatic brain injury (TBI), and good versus poor 3-month functional status (assessed by using the Glasgow Outcome Scale) were also evaluated. vCSF proteins with significant differences between groups were compared by using linear models and selected for gene ontology analysis using R Language and the Panther database. RESULTS: We included 50 patients with ABI (SAH n = 23, TBI n = 15, intracranial hemorrhage n = 6, ischemic stroke n = 3, others n = 3) and 12 patients without ABI. There were significant differences in the expression of 255 proteins between patients with and without ABI (p

Background Acute kidney injury (AKI) requiring renal replacement therapy (RRT) in the ICU portends a poor prognosis. We aimed to better characterize predictors of survival and the mechanism of kidney failure in these patients. Methods Retrospective observational study using clinical and radiological electronic health records, analysed by univariable and multivariable binary logistic regression. Histopathological examination of post-mortem renal tissue was performed. Results Among 157 patients with AKI requiring RRT, higher serum creatinine at RRT initiation associated with increased ICU-survival (OR 0.33, 95%CI 0.17–0.62, p = 0.001) however, muscle mass (a marker of frailty) interacted with creatinine (p = 0.02) and superseded creatinine as a predictor of survival (OR 0.26 95%CI 0.08–0.82; p = 0.02). Achieving lower cumulative fluid balance (mls/kg) predicted ICU-survival (OR 1.01 95%CI 1.00 -1.01, p 500mls/24 hours strongly predicted successful liberation from RRT (OR 0.125, 95%CI 0.05–0.35, p Conclusions Confounding of creatinine by muscle-mass undermines its use as a marker of AKI severity in clinical studies. Volume management and urine-output are key determinants of outcome. Loss of synaptopodin implicates glomerular injury in the pathogenesis of S-AKI.

Critical illness is a continuum, but patient care is often fragmented. Value-based critical care focuses on the overall health of the patient, not on an episode of care. The “ICU without borders” model incorporates a concept where members of the critical care team are involved in the management of patients from the onset of critical illness until recovery and beyond. In this paper, we summarise the potential benefits and challenges to patients, families, staff and the wider healthcare system and list some essential requirements, including a tight governance framework, advanced technologies, investment and trust. We also argue that “ICU without borders” should be viewed as a bi-directional model, allowing extended visiting hours, giving patients and families direct access to experienced critical care staff and offering mutual aid when needed.

Introduction Prognosis after resuscitation from cardiac arrest (CA) remains poor, with high morbidity and mortality as a result of extensive cardiac and brain injury and lack of effective treatments. Hypertonic sodium lactate (HSL) may be beneficial after CA by buffering severe metabolic acidosis, increasing brain perfusion and cardiac performance, reducing cerebral swelling, and serving as an alternative energetic cellular substrate. The aim of this study was to test the effects of HSL infusion on brain and cardiac injury in an experimental model of CA. Methods After a 10-min electrically induced CA followed by 5 min of cardiopulmonary resuscitation maneuvers, adult swine (n = 35) were randomly assigned to receive either balanced crystalloid (controls, n = 11) or HSL infusion started during cardiopulmonary resuscitation (CPR, Intra-arrest, n = 12) or after return of spontaneous circulation (Post-ROSC, n = 11) for the subsequent 12 h. In all animals, extensive multimodal neurological and cardiovascular monitoring was implemented. All animals were treated with targeted temperature management at 34 °C. Results Thirty-four of the 35 (97.1%) animals achieved ROSC; one animal in the Intra-arrest group died before completing the observation period. Arterial pH, lactate and sodium concentrations, and plasma osmolarity were higher in HSL-treated animals than in controls (p p = 0.004). Intra-arrest and Post-ROSC HSL infusion improved hemodynamic status compared to controls, as shown by reduced vasopressor requirements to maintain a mean arterial pressure target > 65 mmHg (p = 0.005 for interaction; p = 0.01 for groups). Moreover, plasma troponin I and glial fibrillary acid protein (GFAP) concentrations were lower in HSL-treated groups at several time-points than in controls. Conclusions In this experimental CA model, HSL infusion was associated with reduced vasopressor requirements and decreased plasma concentrations of measured biomarkers of cardiac and cerebral injury.

Background Alterations in the renin–angiotensin system have been implicated in the pathophysiology of septic shock. In particular, angiotensin 1–7 (Ang-(1–7)), an anti-inflammatory heptapeptide, has been hypothesized to have beneficial effects. The aim of the present study was to test the effects of Ang-(1–7) infusion on the development and severity of septic shock. Methods This randomized, open-label, controlled study was performed in 14 anesthetized and mechanically ventilated sheep. Immediately after sepsis induction by bacterial peritonitis, animals received either Ang-(1–7) (n = 7) or placebo (n = 7) intravenously. Fluid resuscitation, antimicrobial therapy, and peritoneal lavage were initiated 4 h after sepsis induction. Norepinephrine administration was titrated to maintain mean arterial pressure (MAP) between 65 and 75 mmHg. Results There were no differences in baseline characteristics between groups. Septic shock was prevented in 6 of the 7 animals in the Ang-(1–7) group at the end of the 24-h period. Fluid balance and MAP were similar in the two groups; however, MAP was achieved with a mean norepinephrine dose of 0.4 μg/kg/min in the Ang-(1–7) group compared to 4.3 μg/kg/min in the control group. Heart rate and cardiac output index were lower in the Ang (1–7) than in the control group, as were plasma interleukin-6 levels, and creatinine levels. Platelet count and PaO2/FiO2 ratio were higher in the Ang-(1–7) group. Mean arterial lactate at the end of the experiment was 1.6 mmol/L in the Ang-(1–7) group compared to 7.4 mmol/L in the control group. Conclusions In this experimental septic shock model, early Ang-(1–7) infusion prevented the development of septic shock, reduced norepinephrine requirements, limited interleukine-6 increase and prevented renal dysfunction.

IntroductionPrognosis after resuscitated cardiac arrest (CA) remains poor with high morbidity and mortality due to extensive cardiac and brain injuries and the lack of effective treatments. Hypertonic sodium lactate (HSL) could be beneficial after CA by buffering severe metabolic acidosis, increasing brain perfusion and cardiac performance, reducing cerebral swelling, and serving as alternative energetic cellular substrate. The aim of this study was therefore to test the effects of HSL infusion on brain and cardiac injury in an experimental model of CA.MethodsAfter a 10-min electrically induced CA followed by 5 min of cardiopulmonary resuscitation maneuvers, adult swine (n=35) were randomly assigned to receive either balanced crystalloids (controls, n=11) or HSL infusion, either starting during cardiopulmonary resuscitation (CPR, Intra-arrest, n=12) or after return of spontaneous circulation (Post-ROSC, n=11) for the following 12 hours. In all animals, extensive multimodal neurological and cardiovascular monitoring was implemented. All animals were treated with target temperature management at 34°C.Results34 out of 35 (97.1%) animals achieved ROSC and one animal in the Intra-arrest group deceased before completing the observation period. Arterial pH, lactate, sodium concentrations and plasma osmolarity were higher in treated animals then in controls (pConclusionsIn this experimental CA model, HSL infusion was associated with reduced vasopressor requirements and decreased plasmatic levels of biomarkers of cardiac and cerebral injury.

We compared blood pressure (BP) values obtained with a new optical smartphone application (OptiBP™) with BP values obtained using a non-invasive automatic oscillometric brachial cuff (reference method) during the first 2 h of surveillance in a post-anesthesia care unit in patients after non-cardiac surgery. Three simultaneous BP measurements of both methods were recorded every 30 min over a 2-h period. The agreement between measurements was investigated using Bland-Altman and error grid analyses. We also evaluated the performance of the OptiBP™ using ISO81060-2:2018 standards which requires the mean of the differences ± standard deviation (SD) between both methods to be less than 5 mmHg ± 8 mmHg. Of 120 patients enrolled, 101 patients were included in the statistical analysis. The Bland-Altman analysis demonstrated a mean of the differences ± SD between the test and reference methods of + 1 mmHg ± 7 mmHg for mean arterial pressure (MAP), + 2 mmHg ± 11 mmHg for systolic arterial pressure (SAP), and + 1 mmHg ± 8 mmHg for diastolic arterial pressure (DAP). Error grid analysis showed that the proportions of measurement pairs in risk zones A to E were 90.3% (no risk), 9.7% (low risk), 0% (moderate risk), 0% (significant risk), 0% (dangerous risk) for MAP and 89.9%, 9.1%, 1%, 0%, 0% for SAP. We observed a good agreement between BP values obtained by the OptiBP™ system and BP values obtained with the reference method. The OptiBP™ system fulfilled the AAMI validation requirements for MAP and DAP and error grid analysis indicated that the vast majority of measurement pairs (≥ 99%) were in risk zones A and B.Trial Registration ClinicalTrials.gov Identifier: NCT04262323.

The Sequential Organ Failure Assessment (SOFA) score was developed more than 25 years ago to provide a simple method of assessing and monitoring organ dysfunction in critically ill patients. Changes in clinical practice over the last few decades, with new interventions and a greater focus on non-invasive monitoring systems, mean it is time to update the SOFA score. As a first step in this process, we propose some possible new variables that could be included in a SOFA 2.0. By so doing, we hope to stimulate debate and discussion to move toward a new, properly validated score that will be fit for modern practice.

Background During surgery, any mismatch between oxygen delivery (DO2) and consumption (VO2) can promote the development of postoperative complications. The respiratory exchange ratio (RER), defined as the ratio of carbon dioxide (CO2) production (VCO2) to VO2, may be a useful noninvasive tool for detecting inadequate DO2. The primary objective of this study was to test the hypothesis that RER measured during liver transplantation may predict postoperative morbidity. Secondary objectives were to assess the ability of other variables used to assess the DO2/VO2 relationship, including arterial lactate, mixed venous oxygen saturation, and veno-arterial difference in the partial pressure of carbon dioxide (VAPCO2gap), to predict postoperative complications. Methods This retrospective study included consecutive adult patients who underwent liver transplantation for end stage liver disease from June 27th, 2020, to September 5th, 2021. Patients with acute liver failure were excluded. All patients were routinely equipped with a pulmonary artery catheter. The primary analysis was a receiver operating characteristic (ROC) curve constructed to investigate the discriminative ability of the mean RER measured during surgery to predict postoperative complications. RER was calculated at five standardized time points during the surgery, at the same time as measurement of blood lactate levels and arterial and mixed venous blood gases, which were compared as a secondary analysis. Results Of the 115 patients included, 57 developed at least one postoperative complication. The mean RER (median [25–75] percentiles) during surgery was significantly higher in patients with complications than in those without (1.04[0.96–1.12] vs 0.88[0.84–0.94]; p p 2/VO2 relationship (arterial lactate, SvO2, and VAPCO2gap) in predicting postoperative complications. Conclusion During liver transplantation, the RER can reliably predict postoperative complications. Implementing this measure intraoperatively may provide a warning for physicians of impending complications and justify more aggressive optimization of oxygen delivery. Further studies are required to determine whether correcting the RER is feasible and could reduce the incidence of complications.

Background Rapid fluid administration may decrease hemoglobin concentration (Hb) by a diluting effect, which could limit the increase in oxygen delivery (DO2) expected with a positive response to fluid challenge in critically ill patients. Our aim was to quantify the decrease in Hb after rapid fluid administration. Methods Our protocol was registered in PROSPERO (CRD42020165146). We searched PubMed, the Cochrane Database, and Embase from inception until February 15, 2022. We selected studies that reported Hb before and after rapid fluid administration (bolus fluid given over less than 120 min) with crystalloids and/or colloids in adults. Exclusion criteria were studies that included bleeding patients, or used transfusions or extracorporeal circulation procedures. Studies were divided according to whether they involved non-acutely ill or acutely ill (surgical/trauma, sepsis, circulatory shock or severe hypovolemia, and mixed conditions) subjects. The mean Hb difference and, where reported, the DO2 difference before and after fluid administration were extracted. Meta-analyses were conducted to assess differences in Hb before and after rapid fluid administration in all subjects and across subgroups. Random-effect models, meta-regressions and subgroup analyses were performed for meta-analyses. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. Results Sixty-five studies met our inclusion criteria (40 in non-acutely ill and 25 in acutely ill subjects), with a total of 2794 participants. Risk of bias was assessed as “low” for randomized controlled trials (RCTs) and ‘low to moderate’ for non-RCTs. Across 63 studies suitable for meta-analysis, the Hb decreased significantly by a mean of 1.33 g/dL [95% CI − 1.45 to − 1.12; p I2 = 96.88] after fluid administration: in non-acutely ill subjects, the mean decrease was 1.56 g/dL [95% CI − 1.69 to − 1.42 ; p I2 = 96.71] and in acutely ill patients 0.84 g/dL [95% CI − 1.03 to − 0.64; p = 0.033; I2 = 92.91]. The decrease in Hb was less marked in patients with sepsis than in other acutely ill patients. The DO2 decreased significantly in fluid non-responders with a significant decrease in Hb. Conclusions Hb decreased consistently after rapid fluid administration with moderate certainty of evidence. This effect may limit the positive effects of fluid challenges on DO2 and thus on tissue oxygenation.

Sepsis has been recognized for more than 2500 years, but the criteria used to identify it have evolved. Sepsis is an infection associated with some degree of organ dysfunction—put very simplistically, sepsis is a ‘bad infection’. Specific criteria may be useful for research purposes but have less value in day-to-day clinical practice. What is relevant here is early recognition and some awareness of severity so that appropriate therapy can be started without delay.

Purpose: Coronavirus disease–2019 (COVID-19) continues to be a global threat and remains a significant cause of hospitalizations. Recent clinical guidelines have supported the use of corticosteroids or remdesivir in the treatment of COVID-19. However, uncertainty remains about which patients are most likely to benefit from treatment with either drug; such knowledge is crucial for avoiding preventable adverse effects, minimizing costs, and effectively allocating resources. This study presents a machine-learning system with the capacity to identify patients in whom treatment with a corticosteroid or remdesivir is associated with improved survival time. Methods: Gradient-boosted decision-tree models used for predicting treatment benefit were trained and tested on data from electronic health records dated between December 18, 2019, and October 18, 2020, from adult patients (age ≥18 years) with COVID-19 in 10 US hospitals. Models were evaluated for performance in identifying patients with longer survival times when treated with a corticosteroid versus remdesivir. Fine and Gray proportional-hazards models were used for identifying significant findings in treated and nontreated patients, in a subset of patients who received supplemental oxygen, and in patients identified by the algorithm. Inverse probability-of-treatment weights were used to adjust for confounding. Models were trained and tested separately for each treatment. Findings: Data from 2364 patients were included, with men comprising slightly more than 50% of the sample; 893 patients were treated with remdesivir, and 1471 were treated with a corticosteroid. After adjustment for confounding, neither corticosteroids nor remdesivir use was associated with increased survival time in the overall population or in the subpopulation that received supplemental oxygen. However, in the populations identified by the algorithms, both corticosteroids and remdesivir were significantly associated with an increase in survival time, with hazard ratios of 0.56 and 0.40, respectively (both, P = 0.04). Implications: Machine-learning methods have the capacity to identify hospitalized patients with COVID-19 in whom treatment with a corticosteroid or remdesivir is associated with an increase in survival time. These methods may help to improve patient outcomes and allocate resources during the COVID-19 crisis., SCOPUS: ar.j, info:eu-repo/semantics/published

Purpose of review Blood lactate concentrations are frequently measured in critically ill patients and have important prognostic value. Here, we review some key questions related to their clinical use in sepsis. Recent findings Despite the metabolic hurdles, measuring lactate concentrations remains very informative in clinical practice. Although blood lactate levels change too slowly to represent the only guide to resuscitation, serial lactate levels can help to define the patient's trajectory and encourage a review of the therapeutic strategy if they remain stable or increase over time. Summary Lactate concentrations respond too slowly to be used to guide acute changes in therapy, but can help evaluate overall response. Hyperlactatemia should not be considered as a problem in itself, but as a warning of altered cell function.

Management of the patient with sepsis comprises three key branches: control of the underlying infection, haemodynamic stabilization, and modulation of the host response. Each aspect should be considered in all patients and, when relevant, managed at the same time. Infection control is applicable to all patients with sepsis and will include antibiotic therapy and often surgical intervention to remove an infectious source. Haemodynamic support involves fluid administration in all patients and vasoactive agents in patients with associated circulatory shock. Noradrenaline is the first choice vasopressor agent; inotropic agents, usually dobutamine, may be added in case of myocardial depression. No interventions directed at individual components of the host response to sepsis have yet been shown to improve outcomes, but glucocorticoids and vasopressin have a global impact on the response and can thus be considered in this category. A move toward more personalized treatment is needed across all three arms of sepsis management.

Background Angiotensin II is one of the vasopressors available for use in septic shock. However, its effects on the septic myocardium remain unclear. The aim of the study was to compare the effects of angiotensin II and norepinephrine on cardiac function and myocardial oxygen consumption, inflammation and injury in experimental septic shock. Methods This randomized, open-label, controlled study was performed in 20 anesthetized and mechanically ventilated pigs. Septic shock was induced by fecal peritonitis in 16 animals, and four pigs served as shams. Resuscitation with fluids, antimicrobial therapy and abdominal drainage was initiated one hour after the onset of septic shock. Septic pigs were randomly allocated to receive one of the two drugs to maintain mean arterial pressure between 65 and 75 mmHg for 8 h. Results There were no differences in MAP, cardiac output, heart rate, fluid balance or tissue perfusion indices in the two treatment groups but myocardial oxygen consumption was greater in the norepinephrine-treated animals. Myocardial mRNA expression of interleukin-6, interleukin-6 receptor, interleukin-1 alpha, and interleukin-1 beta was higher in the norepinephrine than in the angiotensin II group. Conclusions In septic shock, angiotensin II administration is associated with a similar level of cardiovascular resuscitation and less myocardial oxygen consumption, and inflammation compared to norepinephrine.

Supplemental Digital Content is available in the text., OBJECTIVES: Although early recognition of sepsis is vital to improving outcomes, the diagnosis may be missed or delayed in many patients. Acute kidney injury is one of the most common organ failures in patients with sepsis but may not be apparent on presentation. Novel biomarkers for acute kidney injury might improve organ failure recognition and facilitate earlier sepsis care. DESIGN: Retrospective, international, Sapphire study. SETTING: Academic Medical Center. PATIENTS: Adults admitted to the ICU without evidence of acute kidney injury at time of enrollment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We stratified patients enrolled in the Sapphire study into three groups—those with a clinical diagnosis of sepsis (n = 216), those with infection without sepsis (n = 120), and those without infection (n = 387) at enrollment. We then examined 30-day mortality stratified by acute kidney injury within each group. Finally, we determined the operating characteristics for kidney stress markers (tissue inhibitor of metalloproteinases-2) × (insulin-like growth factor binding protein 7) for prediction of acute kidney injury as a sepsis-defining organ failure in patients with infection without a clinical diagnosis of sepsis at enrollment. Combining all groups, 30-day mortality was 23% for patients who developed stage 2–3 acute kidney injury within the first 3 days compared with 14% without stage 2–3 acute kidney injury. However, this difference was greatest in the infection without sepsis group (34% vs 11%; odds ratio, 4.09; 95% CI, 1.53–11.12; p = 0.005). Using a (tissue inhibitor of metalloproteinases-2) × (insulin-like growth factor binding protein 7) cutoff of 2.0 units, 14 patients (11.7%), in the infection/no sepsis group, tested positive of which 10 (71.4%) developed stage 2–3 acute kidney injury. The positive test result occurred a median of 19 hours (interquartile range, 0.8–34.0 hr) before acute kidney injury manifested by serum creatinine or urine output. Similar results were obtained using a cutoff of 1.0 for any stage of acute kidney injury. CONCLUSIONS: Use of the urinary (tissue inhibitor of metalloproteinases-2) × (insulin-like growth factor binding protein 7) test could identify acute kidney injury in patients with infection, possibly helping to detect sepsis, nearly a day before acute kidney injury is apparent by clinical criteria.

Background: Patients with COVID-19 can develop acute respiratory distress syndrome (ARDS), which is associated with high mortality. The aim of this study was to examine the functional and morphological features of COVID-19-associated ARDS and to compare these with the characteristics of ARDS unrelated to COVID-19. Methods: This prospective observational study was done at seven hospitals in Italy. We enrolled consecutive, mechanically ventilated patients with laboratory-confirmed COVID-19 and who met Berlin criteria for ARDS, who were admitted to the intensive care unit (ICU) between March 9 and March 22, 2020. All patients were sedated, paralysed, and ventilated in volume-control mode with standard ICU ventilators. Static respiratory system compliance, the ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air, ventilatory ratio (a surrogate of dead space), and D-dimer concentrations were measured within 24 h of ICU admission. Lung CT scans and CT angiograms were done when clinically indicated. A dataset for ARDS unrelated to COVID-19 was created from previous ARDS studies. Survival to day 28 was assessed. Findings: Between March 9 and March 22, 2020, 301 patients with COVID-19 met the Berlin criteria for ARDS at participating hospitals. Median static compliance was 41 mL/cm H2O (33–52), which was 28% higher than in the cohort of patients with ARDS unrelated to COVID-19 (32 mL/cm H2O [25–43]; p

Red blood cell transfusions are a frequent intervention in critically ill patients, including in those who are receiving mechanical ventilation. Both these interventions can impact negatively on lung function with risks of transfusion-related acute lung injury (TRALI) and other forms of acute respiratory distress syndrome (ARDS). The interactions between transfusion, mechanical ventilation, TRALI and ARDS are complex and other patient-related (e.g. presence of sepsis or shock, disease severity, and hypervolemia) or blood product-related (e.g. presence of antibodies or biologically active mediators) factors also play a role. We propose several strategies targeted at these factors that may help limit the risks of associated lung injury in critically ill patients being considered for transfusion., SCOPUS: re.j, info:eu-repo/semantics/published

BACKGROUND Optimal transfusion practice remains a matter of ongoing debate despite several large clinical studies. STUDY DESIGN AND METHODS Databases from two observational studies-the Anemia and Blood Transfusion in Critically ill patients (ABC) conducted in 1999 and The Intensive Care Over Nations (ICON) audit conducted in 2012-were compared to evaluate changes in transfusion practice and outcomes over a 13-year period. RESULTS A total of 3534 patients from the ABC study and 4125 from the ICON study were included in this analysis. ICON patients were more severely ill, with higher APACHE II and sequential organ failure assessment (SOFA) scores on admission than ABC patients; however, ICU mortality rates were similar (13.5% vs 13.8%, P = .745). The ICU transfusion rate was significantly lower in the ICON study (24% vs 37%, P

Background: The efficacy and safety of recombinant human soluble thrombomodulin (rhsTM) have not been definitively proven. The effects may depend on the presence of sepsis-associated coagulopathy (SAC). Objectives: The aim of this systematic review and meta-analysis was to evaluate the efficacy and safety of rhsTM in patients with SAC defined by high international normalized ratio and low platelet count. Patients/Methods: EMBASE, MEDLINE, CENTRAL, and clinicaltrial.gov were searched for randomized controlled trials (RCTs) comparing rhsTM with placebo or no treatment in patients with sepsis. The efficacy outcome was 28-day mortality, and the safety outcome was major bleeding. Results: We included 3 RCTs with a total of 1633 patients. Twenty-eight-day mortality was higher in patients with SAC compared with those without SAC (risk ratio [RR] 1.32; 95% confidence intervals [CI], 1.06-1.64). rhsTM was associated with significantly lower 28-day mortality compared with placebo or no treatment in patients with SAC (RR 0.80; 95% CI, 0.65-0.98), but not in those without SAC (RR 1.17; 95% CI, 0.82-1.67) nor in the whole study population (RR 0.88; 95% CI, 0.74-1.04). There was no significant difference in major bleeding between rhsTM and controls in the whole population (RR 1.25; 95% CI, 0.80-1.96), patients with SAC (RR 0.94; 95% CI, 0.45-1.95), and those without SAC (RR 2.26; 95% CI, 0.95-5.35). Conclusions: In patients with sepsis, SAC is associated with higher 28-day mortality. The administration of rhsTM reduced 28-day mortality in patients with SAC, but not in those without SAC.

Background The relationship of PaO2 and PaCO2 levels with outcome after cardiac arrest (CA) is controversial. Few studies have analysed both PaO2 and PaCO2 in this setting and the overall exposure to different PaO2 and PaCO2 levels has not been taken into account. Methods We reviewed blood gas data obtained within the first 24 h from all comatose adult patients who were admitted to the intensive care unit after successful resuscitation from CA. Exposure times to different PaO2 and PaCO2 thresholds were reported as areas under the curve (AUC) and the time above these thresholds was then calculated. The primary outcome measure was neurological outcome assessed using the Cerebral Performance Category (CPC) score at 3 months. An unfavourable outcome was defined as a CPC of 3–5 and a favourable outcome as a CPC of 1–2. Results A total of 356 patients were studied, with a median number of 9 [6–11] blood gas measurements within the first 24 h after admission. The highest and lowest PaO2 and PaCO2 were similar in patients with unfavourable and favourable neurological outcomes. There were no differences in the AUCs or times over different thresholds of PaO2 and PaCO2 in the two groups. In a multivariable analysis, high blood lactate concentrations on admission, presence of shock and a non-shockable initial rhythm were significantly associated with unfavourable outcome. Conclusions There was no association between exposure to various levels of PaO2 and PaCO2 and neurological outcome after cardiac arrest.

Background Arterial hypertension is a worldwide public health problem. While it is currently diagnosed and monitored non-invasively using the oscillometric method, having the ability to measure blood pressure (BP) using a smartphone application could provide more widespread access to hypertension screening and monitoring. In this observational study in intensive care unit patients, we compared blood pressure values obtained using a new optical smartphone application (OptiBP™; test method) with arterial BP values obtained using a radial artery catheter (reference method) in order to help validate the technology. Methods We simultaneously measured three BP values every hour for five consecutive hours on two consecutive days using both the smartphone and arterial methods. Bland–Altman and error grid analyses were used for agreement analysis between both approaches. The performance of the smartphone application was investigated using the Association for the Advancement of Medical Instrumentation (AAMI) and the International Organization for Standardization (ISO) definitions, which require the bias ± SD between two technologies to be below 5 ± 8 mmHg. Results Among the 30 recruited patients, 22 patients had adequate OptiBP™ values and were thus analyzed. In the other 8 patients, no BP could be measured due to inadequate signals. The Bland–Altman analysis revealed a mean of the differences ± SD between both methods of 0.9 ± 7 mmHg for mean arterial pressure (MAP), 0.2 ± 14 mmHg for systolic arterial pressure (SAP), and 1.1 ± 6 mmHg for diastolic arterial pressure (DAP). Error grid analysis demonstrated that the proportions of measurement pairs in risk zones A to E were 88.8% (no risk), 10% (low risk), 1% (moderate risk), 0% (significant risk), and 0% (dangerous risk) for MAP and 88.4%, 8.6%, 3%, 0%, 0%, respectively, for SAP. Conclusions This method comparison study revealed good agreement between BP values obtained using the OptiBP™ and those done invasively. The OptiBP™ fulfills the AAMI/ISO universal standards for MAP and DAP (but not SAP). Error grid showed that the most measurements (≥ 97%) were in risk zones A and B. Trial registration ClinicalTrials.gov registration: NCT04728477

In critically ill patients, fluid infusion is aimed at increasing cardiac output and tissue perfusion. However, it may contribute to fluid overload which may be harmful. Thus, volume status, risks and potential efficacy of fluid administration and/or removal should be carefully evaluated, and monitoring techniques help for this purpose. Central venous pressure is a marker of right ventricular preload. Very low values indicate hypovolemia, while extremely high values suggest fluid harmfulness. The pulmonary artery catheter enables a comprehensive assessment of the hemodynamic profile and is particularly useful for indicating the risk of pulmonary oedema through the pulmonary artery occlusion pressure. Besides cardiac output and preload, transpulmonary thermodilution measures extravascular lung water, which reflects the extent of lung flooding and assesses the risk of fluid infusion. Echocardiography estimates the volume status through intravascular volumes and pressures. Finally, lung ultrasound estimates lung edema. Guided by these variables, the decision to infuse fluid should first consider specific triggers, such as signs of tissue hypoperfusion. Second, benefits and risks of fluid infusion should be weighted. Thereafter, fluid responsiveness should be assessed. Monitoring techniques help for this purpose, especially by providing real time and precise measurements of cardiac output. When decided, fluid resuscitation should be performed through fluid challenges, the effects of which should be assessed through critical endpoints including cardiac output. This comprehensive evaluation of the risk, benefits and efficacy of fluid infusion helps to individualize fluid management, which should be preferred over a fixed restrictive or liberal strategy.

Background Patients with severe mental illness (SMI) (i.e., schizophrenia, bipolar disorder, or major depressive disorder) have been reported to have excess mortality rates from infection compared to patients without SMI, but whether SMI is associated with higher or lower case fatality rates (CFRs) among infected patients remains unclear. The primary objective was to compare the 90-day CFR in septic shock patients with and without SMI admitted to the intensive care unit (ICU), after adjusting for social disadvantage and physical health comorbidity. Methods and findings We conducted a nationwide, population-based cohort study of all adult patients with septic shock admitted to the ICU in France between January 1, 2014, and December 31, 2018, using the French national hospital database. We matched (within hospitals) in a ratio of 1:up to 4 patients with and without SMI (matched-controls) for age (5 years range), sex, degree of social deprivation, and year of hospitalization. Cox regression models were conducted with adjustment for smoking, alcohol and other substance addiction, overweight or obesity, Charlson comorbidity index, presence of trauma, surgical intervention, Simplified Acute Physiology Score II score, organ failures, source of hospital admission (home, transfer from other hospital ward), and the length of time between hospital admission and ICU admission. The primary outcome was 90-day CFR. Secondary outcomes were 30- and 365-day CFRs, and clinical profiles of patients. A total of 187,587 adult patients with septic shock admitted to the ICU were identified, including 3,812 with schizophrenia, 2,258 with bipolar disorder, and 5,246 with major depressive disorder. Compared to matched controls, the 90-day CFR was significantly lower in patients with schizophrenia (1,052/3,269 = 32.2% versus 5,000/10,894 = 45.5%; adjusted hazard ratio (aHR) = 0.70, 95% confidence interval (CI) 0.65,0.75, p < 0.001), bipolar disorder (632/1,923 = 32.9% versus 2,854/6,303 = 45.3%; aHR = 0.70, 95% CI = 0.63,0.76, p < 0.001), and major depressive disorder (1,834/4,432 = 41.4% versus 6,798/14,452 = 47.1%; aHR = 0.85, 95% CI = 0.81,0.90, p < 0.001). Study limitations include inability to capture deaths occurring outside hospital, lack of data on processes of care, and problems associated with missing data and miscoding in medico-administrative databases. Conclusions Our findings suggest that, after adjusting for social disadvantage and physical health comorbidity, there are improved septic shock outcome in patients with SMI compared to patients without. This finding may be the result of different immunological profiles and exposures to psychotropic medications, which should be further explored.

Background A mismatch between oxygen delivery (DO2) and consumption (VO2) is associated with increased perioperative morbidity and mortality. Hyperlactatemia is often used as an early screening tool, but this non-continuous measurement requires intermittent arterial line sampling. Having a non-invasive tool to rapidly detect inadequate DO2 is of great clinical relevance. The respiratory exchange ratio (RER) can be easily measured in all intubated patients and has been shown to predict postoperative complications. We therefore aimed to assess the discriminative ability of the RER to detect an inadequate DO2 as reflected by hyperlactatemia in patients having intermediate-to-high risk abdominal surgery. Methods This historical cohort study included all consecutive patients who underwent intermediate-to-high risk surgery from January 1st, 2014, to April 30th, 2019 except those who did not have RER and/or arterial lactate measured. Blood lactate levels were measured routinely at the beginning and end of surgery and RER was calculated at the same moment as the blood gas sampling. The present study tested the hypothesis that RER measured at the end of surgery could detect hyperlactatemia at that time. A receiver operating characteristic (ROC) curve was constructed to assess if RER calculated at the end of the surgery could detect hyperlactatemia. The chosen RER threshold corresponded to the highest value of the sum of the specificity and the sensitivity (Youden Index). Results Among the 996 patients available in our study cohort, 941 were included and analyzed. The area under the ROC curve was 0.73 (95% CI: 0.70 to 0.76; p 1.5 mmol/L with a sensitivity of 87.5% and a specificity of 49.5%. Conclusion In mechanically ventilated patients undergoing intermediate to high-risk abdominal surgery, the RER had moderate discriminative abilities to detect hyperlactatemia. Increased values should prompt clinicians to investigate for the presence of hyperlactatemia and treat any potential causes of DO2/VO2 mismatch as suggested by the subsequent presence of hyperlactatemia.

Intensive care units (ICUs) around the world have been hugely impacted by the SARS-CoV-2 pandemic and the vast numbers of patients admitted with COVID-19, requiring respiratory support and prolonged stays. This pressure, with resulting shortages of ICU beds, equipment, and staff has raised ethical dilemmas as physicians have had to determine how best to allocate the sparse resources. Here, we reflect on some of the major ethical aspects of the COVID-19 pandemic, including resource allocation and rationing, end-of-life decision-making, and communication and staff support. Importantly, these issues are regularly faced in non-pandemic ICU patient management and useful lessons can be learned from the discussions that have occurred as a result of the COVID-19 situation.

BACKGROUND: Vasopressors are a cornerstone for the management of vasodilatory hypotension. Vasopressor infusions are currently adjusted manually to achieve a predefined arterial pressure target. We have developed a closed-loop vasopressor (CLV) controller to help correct hypotension more efficiently during the perioperative period. We tested the hypothesis that patients managed using such a system postcardiac surgery would present less hypotension compared to patients receiving standard management. METHODS: A total of 40 patients admitted to the intensive care unit (ICU) after cardiac surgery were randomized into 2 groups for a 2-hour study period. In all patients, the objective was to maintain mean arterial pressure (MAP) between 65 and 75 mm Hg using norepinephrine. In the CLV group, the norepinephrine infusion was controlled via the CLV system; in the control group, it was adjusted manually by the ICU nurse. Fluid administration was standardized in both groups using an assisted fluid management system linked to an advanced hemodynamic monitoring system. The primary outcome was the percentage of time patients were hypotensive, defined as MAP 75 mm Hg (and norepinephrine still being infused) was also significantly lower in patients in the CLV group than that in the control group (3.2% [1.9–5.4] vs 20.6% [8.9–32.5]; location difference, −17% [95% CI, −10 to −24]; P < .001). The number of norepinephrine infusion rate modifications over the study period was greater in the CLV group than that in the control group (581 [548–597] vs 13 [11–14]; location difference, 568 [578–538]; P < .001). No adverse event occurred during the study period in both groups. CONCLUSIONS: Closed-loop control of norepinephrine infusion significantly decreases postoperative hypotension compared to manual control in patients admitted to the ICU after cardiac surgery. (Anesth Analg 2022;134:964–73)

Background Little is known about the prevalence of altered CAR in anoxic brain injury and the association with patients’ outcome. We aimed at investigating CAR in cardiac arrest survivors treated by targeted temperature management and its association to outcome. Methods Retrospective analysis of prospectively collected data. Inclusion criteria: adult cardiac arrest survivors treated by targeted temperature management (TTM). Exclusion criteria: trauma; sepsis, intoxication; acute intra-cranial disease; history of supra-aortic vascular disease; severe hemodynamic instability; cardiac output mechanical support; arterial carbon dioxide partial pressure (PaCO2) > 60 mmHg; arrhythmias; lack of acoustic window. Middle cerebral artery flow velocitiy (FV) was assessed by transcranial Doppler (TCD) once during hypothermia (HT) and once during normothermia (NT). FV and blood pressure (BP) were recorded simultaneously and Mxa calculated (MATLAB). Mxa is the Pearson correlation coefficient between FV and BP. Mxa > 0.3 defined altered CAR. Survival was assessed at hospital discharge. Cerebral Performance Category (CPC) 3–5 assessed 3 months after CA defined unfavorable neurological outcome (UO). Results We included 50 patients (Jan 2015–Dec 2018). All patients had out-of-hospital cardiac arrest, 24 (48%) had initial shockable rhythm. Time to return of spontaneous circulation was 20 [10–35] min. HT (core body temperature 33.7 [33.2–34] °C) lasted for 24 [23–28] h, followed by rewarming and NT (core body temperature: 36.9 [36.6–37.4] °C). Thirty-one (62%) patients did not survive at hospital discharge and 36 (72%) had UO. Mxa was lower during HT than during NT (0.33 [0.11–0.58] vs. 0.58 [0.30–0.83]; p = 0.03). During HT, Mxa did not differ between outcome groups. During NT, Mxa was higher in patients with UO than others (0.63 [0.43–0.83] vs. 0.31 [− 0.01–0.67]; p = 0.03). Mxa differed among CPC values at NT (p = 0.03). Specifically, CPC 2 group had lower Mxa than CPC 3 and 5 groups. At multivariate analysis, initial non-shockable rhythm, high Mxa during NT and highly malignant electroencephalography pattern (HMp) were associated with in-hospital mortality; high Mxa during NT and HMp were associated with UO. Conclusions CAR is frequently altered in cardiac arrest survivors treated by TTM. Altered CAR during normothermia was independently associated with poor outcome.

BACKGROUND Although fluid administration is a key strategy to optimise haemodynamic status and tissue perfusion, optimal fluid administration during liver surgery remains controversial. OBJECTIVE To test the hypothesis that a goal-directed fluid therapy (GDFT) strategy, when compared with a conventional fluid strategy, would better optimise systemic blood flow and lead to improved urethral tissue perfusion (a new variable to assess peripheral blood flow), without increasing blood loss. DESIGN Single-centre prospective randomised controlled superiority study. SETTING Erasme Hospital. PATIENTS Patients undergoing liver surgery. INTERVENTION Forty patients were randomised into two groups: all received a basal crystalloid infusion (maximum 2 ml kg-1 h-1). In the conventional fluid group, the goal was to maintain central venous pressure (CVP) as low as possible during the dissection phase by giving minimal additional fluid, while in the posttransection phase, anaesthetists were free to compensate for any presumed fluid deficit. In the GDFT group, patients received in addition to the basal infusion, multiple minifluid challenges of crystalloid to maintain stroke volume (SV) variation less than 13%. Noradrenaline infusion was titrated to keep mean arterial pressure more than 65 mmHg in all patients. MAIN OUTCOME MEASURE The mean intra-operative urethral perfusion index. RESULTS The mean urethral perfusion index was significantly higher in the GDFT group than in the conventional fluid group (8.70 [5.72 to 13.10] vs. 6.05 [4.95 to 8.75], P = 0.046). SV index (ml m-2) and cardiac index (l min-1 m-2) were higher in the GDFT group (48 ± 9 vs. 33 ± 7 and 3.5 ± 0.7 vs. 2.4 ± 0.4, respectively; P

To investigate whether an increase in skin blood flow (SBF) after fluid challenge was associated with an increase in oxygen consumption (VOWe studied 62 patients with shock who required fluid challenge. Using laser Doppler, we measured finger SBF at basal temperature (SBFOf the 62 patients, 33 were fluid responders and 16 of these were VOA lower baseline SBF

Life expectancy is rising worldwide and increasing numbers of elderly patients are being admitted to the intensive care unit (ICU). Because ageing is associated with changes in organ function, increased frailty, reduced activities of daily living, reduced mobility, and reduced cognition, elderly patients represent a particular subgroup of ICU patients. Ethical decisions related to the appropriateness of intensive care and/or life-sustaining interventions, the withdrawing and withholding of life support, and terminal sedation are more frequent in these patients and will be discussed in this review. Such decisions must be tailored to the individual to take into consideration personal beliefs and wishes.

To describe international variation in interprofessional rounds in intensive care units (ICUs).Survey of ICU clinicians on their practices and perceptions of rounds using societal mailing lists and social media.Out of 2402 respondents, 1752 (72.8%) use rounds. Teams are mostly composed of intensivists, nurses and medical trainees. The majority of rounds (57.5%) last2 h, and North Americans report the highest rates of rounds allowing family attendance (92.4%). Shorter rounds (1-2 h, OR 0.67, 0.52-0.86, p 0.01;1 h, OR 0.72, 0.53-0.97, p = 0.03), and strategies such as designating a person for writing (OR 0.73, 0.57-0.95, p = 0.01), and designating a person to assist other patients (OR 0.75, 0.57-0.98, p = 0.04) are associated with a lower perception of negative outcomes. Using daily goals during rounds is associated with a higher perception of positive outcomes (OR 1.85, 1.17-2.90, p 0.01).Three-quarters of respondents perform rounds, and models of rounds are heterogeneous, creating challenges for future studies on improving rounds. Respondents reporting better outcomes also experience shorter rounds, and adopt strategies such as discussion of daily goals, and designation individuals for writing or assisting other patients during rounds.

Numerous compounds have been tested as potential biomarkers for multiple possible applications within intensive care medicine but none is or will ever be sufficiently specific or sensitive for the heterogeneous syndromes of critical illness. New technology and access to huge patient databases are providing new biomarker options and the focus is shifting to combinations of several or multiple biomarkers rather than the single markers that research has concentrated on in the past. Biomarkers will increasingly be used as part of routine clinical practice in the future, complementing clinical examination and physician expertise to provide accurate disease diagnosis, prediction of complications, personalized treatment guidance, and prognosis.

Objectives:To determine which multicenter randomized controlled trials in critically ill patients have shown that the study intervention was associated with a statistically significant reduction in mortality. Our analysis provides an update to a report published 10 years ago.Data Sources:MEDLINE dat

International audience; Wired electrocardiogram monitors are an important component of current perioperative monitoring. Wireless monitoring units could help reduce the number of cables attached to patients and thus improve anesthesia ergonomics and patient management. However, there is concern that electromagnetic interference generated by electrosurgical units may prevent effective wireless signals in the operating room. To evaluate the extent of this problem, we developed a Bluetooth electrocardiogram prototype monitor and compared its electrocardiogram traces to those captured with a standard wired electrocardiogram monitor in our operating room. METHODS: Bluetooth electrocardiogram and standard electrocardiogram traces captured from 10 patients undergoing surgical procedures that required use of an electrosurgical unit were compared by analysis of the durations of the P wave, QRS complex, and T wave and the position of the ST segment from the isoelectric line. The impact of the electrosurgical units on the Bluetooth electrocardiogram and S-electrocardiogram recordings was also assessed. RESULTS: There were no clinically relevant differences in P wave, QRS complex, or T-wave durations (0.006, 0.004, and 0.017 seconds, respectively) between Bluetooth electrocardiogram and standard electrocardiogram or in the position of the ST segment from the isoelectric line (0.02 mV). Mean differences were near zero, and Bland-Altman limits of agreement for individual differences were narrow (-0.035 to 0.047, -0.03 to 0.038, and -0.112 to 0.078 seconds for P wave, QRS complex, and T-wave durations, respectively, and -0.13 to 0.17 mV for ST segment position). Electrosurgical units use electrically disrupted Bluetooth electrocardiogram and standard electrocardiogram signals, but there was no electromagnetic interference effect on the Bluetooth electrocardiogram signals. CONCLUSIONS: Wireless electrocardiogram using Bluetooth can be reliably used in the operating room. The electrosurgical unit induces electric rather than electromagnetic artifacts, thus affecting wired and wireless electrocardiogram in a similar fashion.

Introduction: Despite considerable advances in our understanding of how sepsis develops and multiple clinical trials of potential therapies, no new pharmacologic agent has been consistently shown to improve survival. Areas covered: We reviewed relevant publications identified through PubMed and from the authors' knowledge of this field. We discuss the main reasons why clinical trials on new therapeutic interventions have failed in the past, including heterogeneity of study populations and choice of outcome measures. We discuss how changes in study design and in patient selection could help improve identification of effective agents in the future. Expert opinion: The search for new sepsis therapies must continue but lessons must be learned from previous clinical trials so that the same mistakes are not repeated. Rather than grouping all patients with sepsis together, we should study only those most likely to benefit from the intervention. Better characterization of patients will be facilitated using modern 'omics technology and analysis of the increasingly large quantities of clinical data available, enabling more personalized patient selection for trial inclusion. New clinical trial design and inclusion of other endpoints in addition to mortality will also aid our search for the elusive positive clinical trial and effective interventions for sepsis.

Fluid therapy, which is provided to restore and maintain tissue perfusion, is part of routine management for almost all critically ill patients. However, because either too much or too little fluid can have a negative impact on patient outcomes, fluid administration must be titrated carefully for each patient. The “salvage, optimization, stabilization, de-escalation” (SOSD) mnemonic should be used as a general guide to fluid resuscitation, and fluid administration should be adapted according to the course of the disease. In the initial salvage phase, lifesaving fluid should be administered generously. Once hemodynamic monitoring is available, fluid administration should be optimized by determining the patient's fluid status and the need for further fluid. This determination can be difficult, however; clinical indicators of hypovolemia, such as heart rate, blood pressure, and urine output, may not detect early hypovolemia, and edema is a late sign of fluid overload. Dynamic tests of fluid responsiveness such as pulse pressure or stroke volume variation can be used in only a small percentage of critically ill patients, and thus a fluid challenge technique is most frequently used to assess ongoing fluid requirements. Once a patient has been stabilized, efforts should start to concentrate on removing excess fluid. Which fluid should be used remains a matter of some debate. Crystalloid solutions are cheaper than colloid solutions, but colloid solutions remain in the intravascular space for a longer period, making edema less likely. Thus crystalloids and colloids should be used together, especially in patients likely to require large fluid volumes. Human albumin is a natural colloid and may have beneficial effects in patients with sepsis in addition to its volume effects. Fluids should be prescribed as are other medications, taking into account individual patient factors, disease processes, and other treatments., SCOPUS: re.j, info:eu-repo/semantics/published

Acute kidney injury (AKI) occurs in approximately 20% of hospitalized patients and is associated with increased morbidity and mortality. The care of hospitalized patients with AKI has been shown to be variable in clinical practices. Systematic tools including checklists, care bundles and medical algorithms have been developed and implemented to improve the care and outcomes of AKI patients. However, whether these systematic tools can improve the quality of care and outcomes of AKI patients is still unknown. The committee of the 19th Acute Disease Quality Initiative (ADQI) conference dedicated a workgroup with the task of developing a study protocol to investigate this question. A comprehensive literature search was performed using PubMed and Embase. Key questions and feasibility of potential study proposals were discussed during the conference. Then a two-step Delphi process was used to reach consensus regarding several aspects of the study protocol. The group suggested that patient risk assessment be included in the study protocol and the choice of systematic tool be depending on different clinical contexts. The group also proposed a two-phase study with the use of oliguria and systematic tool to investigate the quality of care and outcomes of AKI patients. Consensus was reached on a study protocol regarding the efficacy of using systematic tools to improve clinical management and outcomes of AKI patients.