Macrophage expression and prognostic significance of the long pentraxin PTX3 in COVID-19.

Long pentraxin 3 (PTX3) is an essential component of humoral innate immunity, involved in resistance to selected pathogens and in the regulation of inflammation1-3. The present study was designed to assess the presence and significance of PTX3 in Coronavirus Disease 2019 (COVID-19)4-7. RNA-sequencing analysis of peripheral blood mononuclear cells, single-cell bioinformatics analysis and immunohistochemistry of lung autopsy samples revealed that myelomonocytic cells and endothelial cells express high levels of PTX3 in patients with COVID-19. Increased plasma concentrations of PTX3 were detected in 96 patients with COVID-19. PTX3 emerged as a strong independent predictor of 28-d mortality in multivariable analysis, better than conventional markers of inflammation, in hospitalized patients with COVID-19. The prognostic significance of PTX3 abundance for mortality was confirmed in a second independent cohort (54 patients). Thus, circulating and lung myelomonocytic cells and endothelial cells are a major source of PTX3, and PTX3 plasma concentration can serve as an independent strong prognostic indicator of short-term mortality in COVID-19.

Simvastatin in Critically Ill Patients with Covid-19.

BACKGROUND: The efficacy of simvastatin in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: In an ongoing international, multifactorial, adaptive platform, randomized, controlled trial, we evaluated simvastatin (80 mg daily) as compared with no statin (control) in critically ill patients with Covid-19 who were not receiving statins at baseline. The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors; the analyis used a Bayesian hierarchical ordinal model. The adaptive design included prespecified statistical stopping criteria for superiority (>99% posterior probability that the odds ratio was >1) and futility (>95% posterior probability that the odds ratio was <1.2). RESULTS: Enrollment began on October 28, 2020. On January 8, 2023, enrollment was closed on the basis of a low anticipated likelihood that prespecified stopping criteria would be met as Covid-19 cases decreased. The final analysis included 2684 critically ill patients. The median number of organ support-free days was 11 (interquartile range, -1 to 17) in the simvastatin group and 7 (interquartile range, -1 to 16) in the control group; the posterior median adjusted odds ratio was 1.15 (95% credible interval, 0.98 to 1.34) for simvastatin as compared with control, yielding a 95.9% posterior probability of superiority. At 90 days, the hazard ratio for survival was 1.12 (95% credible interval, 0.95 to 1.32), yielding a 91.9% posterior probability of superiority of simvastatin. The results of secondary analyses were consistent with those of the primary analysis. Serious adverse events, such as elevated levels of liver enzymes and creatine kinase, were reported more frequently with simvastatin than with control. CONCLUSIONS: Although recruitment was stopped because cases had decreased, among critically ill patients with Covid-19, simvastatin did not meet the prespecified criteria for superiority to control. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.).

Restriction of Intravenous Fluid in ICU Patients with Septic Shock.

BACKGROUND: Intravenous fluids are recommended for the treatment of patients who are in septic shock, but higher fluid volumes have been associated with harm in patients who are in the intensive care unit (ICU). METHODS: In this international, randomized trial, we assigned patients with septic shock in the ICU who had received at least 1 liter of intravenous fluid to receive restricted intravenous fluid or standard intravenous fluid therapy; patients were included if the onset of shock had been within 12 hours before screening. The primary outcome was death from any cause within 90 days after randomization. RESULTS: We enrolled 1554 patients; 770 were assigned to the restrictive-fluid group and 784 to the standard-fluid group. Primary outcome data were available for 1545 patients (99.4%). In the ICU, the restrictive-fluid group received a median of 1798 ml of intravenous fluid (interquartile range, 500 to 4366); the standard-fluid group received a median of 3811 ml (interquartile range, 1861 to 6762). At 90 days, death had occurred in 323 of 764 patients (42.3%) in the restrictive-fluid group, as compared with 329 of 781 patients (42.1%) in the standard-fluid group (adjusted absolute difference, 0.1 percentage points; 95% confidence interval [CI], -4.7 to 4.9; P = 0.96). In the ICU, serious adverse events occurred at least once in 221 of 751 patients (29.4%) in the restrictive-fluid group and in 238 of 772 patients (30.8%) in the standard-fluid group (adjusted absolute difference, -1.7 percentage points; 99% CI, -7.7 to 4.3). At 90 days after randomization, the numbers of days alive without life support and days alive and out of the hospital were similar in the two groups. CONCLUSIONS: Among adult patients with septic shock in the ICU, intravenous fluid restriction did not result in fewer deaths at 90 days than standard intravenous fluid therapy. (Funded by the Novo Nordisk Foundation and others; CLASSIC ClinicalTrials.gov number, NCT03668236.).

In-Hospital Violence and Its Impact on Critical Care Practitioners.

OBJECTIVES: To provide a narrative review of hospital violence (HV) and its impact on critical care clinicians. DATA SOURCES: Detailed search strategy using PubMed and OVID Medline for English language articles describing HV, risk factors, precipitating events, consequences, and mitigation strategies. STUDY SELECTION: Studies that specifically addressed HV involving critical care medicine clinicians or their practice settings were selected. The time frame was limited to the last 15 years to enhance relevance to current practice. DATA EXTRACTION: Relevant descriptions or studies were reviewed, and abstracted data were parsed by setting, clinician type, location, social media events, impact, outcomes, and responses (agency, facility, health system, individual). DATA SYNTHESIS: HV is globally prevalent, especially in complex care environments, and correlates with a variety of factors including ICU stay duration, conflict, and has recently expanded to out-of-hospital occurrences; online violence as well as stalking is increasingly prevalent. An overlap with violent extremism and terrorism that impacts healthcare facilities and clinicians is similarly relevant. A number of approaches can reduce HV occurrence including, most notably, conflict management training, communication initiatives, and visitor flow and access management practices. Rescue training for HV occurrences seems prudent. CONCLUSIONS: HV is a global problem that impacts clinicians and imperils patient care. Specific initiatives to reduce HV drivers include individual training and system-wide adaptations. Future methods to identify potential perpetrators may leverage machine learning/augmented intelligence approaches.

The effect of passive leg raising test on intracranial pressure and cerebral autoregulation in brain injured patients: a physiological observational study.

BACKGROUND: The use of the passive leg raising (PLR) is limited in acute brain injury (ABI) patients with increased intracranial pressure (ICP) since the postural change of the head may impact on ICP and cerebral autoregulation. However, the PLR use may prevent a positive daily fluid balance, which had been recently associated to worse neurological outcomes. We therefore studied early and delayed effects of PLR on the cerebral autoregulation of patients recovering from ABI. MATERIALS AND METHODS: This is a Prospective, observational, single-center study conducted in critically ill patients admitted with stable ABI and receiving invasive ICP monitoring, multimodal neuromonitoring and continuous hemodynamic monitoring. The fluid challenge consisted of 500 mL of crystalloid over 10 min; fluid responsiveness was defined as cardiac index increase ≥ 10%. Comparisons between different variables at baseline and after PLR were made by paired Wilcoxon signed-rank test. The correlation coefficients between hemodynamic and neuromonitoring variables were assessed using Spearman's rank test. RESULTS: We studied 23 patients [12 patients (52.2%) were fluid responders]. The PLR significantly increased ICP [from 13.7 (8.3-16.4) to 15.4 (12.0-19.2) mmHg; p < 0.001], cerebral perfusion pressure (CPP) [from 51.1 (47.4-55.6) to 56.4 (49.6-61.5) mmHg; p < 0.001] and the pressure reactivity index (PRx) [from 0.12 (0.01-0.24) to 0.43 (0.34-0.46) mmHg; p < 0.001]. Regarding Near Infrared Spectroscopy (NIRS)-derived parameters, PLR significantly increased the arterial component of regional cerebral oxygen saturation (O2Hbi) [from 1.8 (0.8-3.7) to 4.3 (2.5-5.6) µM cm; p < 0.001], the deoxygenated hemoglobin (HHbi) [from 1.6 (0.2-2.9) to 2.7 (1.4-4.0) µM cm; p = 0.007] and total hemoglobin (cHbi) [from 3.6 (1.9-5.3) to 7.8 (5.2-10.3): p < 0.001]. In all the patients who had altered autoregulation after PLR, these changes persisted ten minutes afterwards. After the PLR, we observed a significant correlation between MAP and CPP and PRx. CONCLUSIONS: In ABI patient with stable ICP, PLR test increased ICP, but mostly within safety values and thresholds. Despite this, cerebral autoregulation was importantly impaired, and this persisted up to 10 min after the end of the maneuvre. Our results discourage the use of PLR test in ABI even when ICP is stable.

Evaluating tranexamic acid for the prevention and treatment of obstetric hemorrhage.

PURPOSE OF REVIEW: Tranexamic acid (TXA) has emerged as a promising pharmacological adjunct to treat and prevent postpartum hemorrhage (PPH). We provide an overview of TXA, including its pharmacology, key findings of randomized trials and observational studies, and critical patient safety information. RECENT FINDINGS: Pharmacokinetic data indicate that TXA infusions result in peak plasma concentration within 3 min (range: 1-6.6 min). Ex-vivo pharmacodynamic data suggest that low-dose TXA (5 mg/kg) inhibits maximum lysis for at least 1 h. In predominantly developing countries, TXA has demonstrated a 19% reduction in the risk of bleeding-related death among patients with PPH. Based on high-quality randomized trials, TXA prophylaxis does not effectively reduce the risk of PPH during vaginal delivery and is likely ineffective in reducing the PPH risk during cesarean delivery. TXA exposure does not increase the risk of maternal thrombotic events. Maternal deaths have occurred from accidental intrathecal TXA injection from look-alike medication errors. SUMMARY: TXA has shown promise as an important adjunct for PPH treatment, especially in low-resource settings. However, TXA is not recommended as PPH prophylaxis during vaginal or cesarean delivery. Patient safety initiatives should be prioritized to prevent maternal death from accidental intrathecal TXA injection.

30-day mortality among very old patients admitted to European intensive care units for major trauma.

INTRODUCTION: Cases of major trauma in the very old (over 80 years) are increasingly common in the intensive care unit. Predicting outcome is challenging in this group of patients as chronological age is a poor marker of health and poor predictor of outcome. Increasingly, decisions are guided with the use of organ dysfunction scores of both the acute condition (e.g. Sequential Organ Failure Assessment (SOFA) score) and chronic health issues (e.g. clinical frailty scale, (CFS)). Recent work suggests that increased CFS is associated with a worse outcome in elderly major trauma patients. We aimed to test whether this association held true in the very old (over 80) or whether SOFA had a stronger association with 30-day outcome. METHODS: Data from the VIP-1 and VIP-2 studies for patients over 80 years old with major trauma admissions were merged. These participants were recruited from 20 countries across Europe. Baseline characteristics, level of care provided and outcome (ICU and 30-day mortality) were summarised. Uni- and multi- variable regression analysis were undertaken to determine associations between CFS and SOFA score in the first 24-hours, type of major trauma and outcomes. RESULTS: Of the 8062 acute patients recruited to the two VIP studies, 498 patients were admitted to intensive care because of major trauma. Median age was 84 years; median SOFA score was 6 (IQR 3,9) and median CFS was 3 (IQR 2,5). Survival to 30-days was 54%. Median and inter-quartile range of CFS was the same in survivors and non-survivors. In the logistic regression analysis, CFS was not associated with increased mortality. SOFA score (p<0.001) and trauma with head injury (p<0.01) were associated with increased mortality. CONCLUSIONS: Major trauma admissions in the very old are not uncommon and 30-day mortality is high. We found that CFS was not a helpful predictor of mortality. SOFA and trauma with head injury were associated with worse outcomes in this patient group.

Effect of decreasing PEEP on hyperinflation and collapse in COVID-19: A computed tomography study.

BACKGROUND: High positive end-expiratory pressure (PEEP>10 cmH2O) is commonly used in mechanically ventilated hypoxemic patients with COVID-19. However, some epidemiological and physiological studies indirectly suggest that using a lower PEEP may primarily and beneficially decrease lung hyperinflation in this population. Herein we directly quantified the effect of decreasing PEEP from 15 to 10 cmH2O on lung hyperinflation and collapse in mechanically ventilated patients with COVID-19. METHODS: Twenty mechanically ventilated patients with COVID-19 underwent a lung computed tomography (CT) at PEEP of 15 and 10 cmH2O. The effect of decreasing PEEP on lung hyperinflation and collapse was directly quantified as the change in the over-aerated (density below -900 HU) and non-aerated (density above -100 HU) lung volumes. The net response to decreasing PEEP was computed as the sum of the change in those two compartments and expressed as the change in the "pathologic" lung volume. If the pathologic lung volume decreased (i.e., hyperinflation decreased more than collapse increased) when PEEP was decreased, the net response was considered positive; otherwise, it was considered negative. RESULTS: On average, the ratio of arterial tension to inspiratory fraction of oxygen (PaO2:FiO2) in the overall study population was 137 (119-162) mmHg. In 11 (55%) patients, the net response to decreasing PEEP was positive. Their over-aerated lung volume decreased by 159 (98-186) mL, while the non-aerated lung volume increased by only 58 (31-91) mL. In nine (45%) patients, the net response was negative. Their over-aerated lung volume decreased by 46 (18-72) mL, but their non-aerated lung volume increased by 107 (44-121) mL. CONCLUSION: In 20 patients with COVID-19 the net response to decreasing PEEP, as assessed with lung CT, was variable. In approximately half of them it was positive (and possibly beneficial), with a decrease in hyperinflation larger than the increase in collapse.

Albumin use in patients with septic shock-Post-hoc analyses of an international randomised fluid trial.

BACKGROUND: Albumin administration is suggested in patients with sepsis and septic shock who have received large volumes of crystalloids. Given lack of firm evidence, clinical practice variation may exist. To address this, we investigated if patient characteristics or trial site were associated with albumin use in septic shock. METHODS: We conducted a post-hoc study of the CLASSIC international, randomised clinical trial of fluid volumes in septic shock. Associations between selected baseline variables and trial site with albumin use during ICU stay were assessed in Cox models considering death, ICU discharge, and loss-to-follow-up as competing events. Baseline variables were first assessed individually, adjusted for treatment allocation (restrictive vs. standard IV fluid), and then adjusted for allocation and the other baseline variables. Site was assessed in a model adjusted for allocation and baseline variables. RESULTS: We analysed 1541 of 1554 patients randomised in CLASSIC (99.2%). During ICU stay, 36.3% of patients in the restrictive-fluid group and 52.6% in the standard-fluid group received albumin. Gastrointestinal focus of infection and higher doses of norepinephrine were most strongly associated with albumin use (subgroup with highest quartile of norepinephrine doses, hazard ratio (HR) 2.58, 95% CI 1.89 to 3.53). HRs for associations between site and albumin use ranged from 0.11 (95% CI 0.05 to 0.26) to 1.70 (95% CI 1.06 to 2.74); test for overall effect of site: p < .001. CONCLUSIONS: In adults with septic shock, gastrointestinal focus of infection and higher doses of norepinephrine at baseline were associated with albumin use, which also varied substantially between sites.

Restrictive versus standard IV fluid therapy in adult ICU patients with septic shock-Bayesian analyses of the CLASSIC trial.

BACKGROUND: The CLASSIC trial assessed the effects of restrictive versus standard intravenous (IV) fluid therapy in adult intensive care unit (ICU) patients with septic shock. This pre-planned study provides a probabilistic interpretation and evaluates heterogeneity in treatment effects (HTE). METHODS: We analysed mortality, serious adverse events (SAEs), serious adverse reactions (SARs) and days alive without life-support within 90 days using Bayesian models with weakly informative priors. HTE on mortality was assessed according to five baseline variables: disease severity, vasopressor dose, lactate levels, creatinine values and IV fluid volumes given before randomisation. RESULTS: The absolute difference in mortality was 0.2%-points (95% credible interval: -5.0 to 5.4; 47% posterior probability of benefit [risk difference <0.0%-points]) with restrictive IV fluid. The posterior probabilities of benefits with restrictive IV fluid were 72% for SAEs, 52% for SARs and 61% for days alive without life-support. The posterior probabilities of no clinically important differences (absolute risk difference ≤2%-points) between the groups were 56% for mortality, 49% for SAEs, 90% for SARs and 38% for days alive without life-support. There was 97% probability of HTE for previous IV fluid volumes analysed continuously, that is, potentially relatively lower mortality of restrictive IV fluids with higher previous IV fluids. No substantial evidence of HTE was found in the other analyses. CONCLUSION: We could not rule out clinically important effects of restrictive IV fluid therapy on mortality, SAEs or days alive without life-support, but substantial effects on SARs were unlikely. IV fluids given before randomisation might interact with IV fluid strategy.

Effects of IV fluid restriction according to site-specific intensity of standard fluid treatment-protocol.

BACKGROUND: Variation in usual practice in fluid trials assessing lower versus higher volumes may affect overall comparisons. To address this, we will evaluate the effects of heterogeneity in treatment intensity in the Conservative versus Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care trial. This will reflect the effects of differences in site-specific intensities of standard fluid treatment due to local practice preferences while considering participant characteristics. METHODS: We will assess the effects of heterogeneity in treatment intensity across one primary (all-cause mortality) and three secondary outcomes (serious adverse events or reactions, days alive without life support and days alive out of hospital) after 90 days. We will classify sites based on the site-specific intensity of standard fluid treatment, defined as the mean differences in observed versus predicted intravenous fluid volumes in the first 24 h in the standard-fluid group while accounting for differences in participant characteristics. Predictions will be made using a machine learning model including 22 baseline predictors using the extreme gradient boosting algorithm. Subsequently, sites will be grouped into fluid treatment intensity subgroups containing at least 100 participants each. Subgroups differences will be assessed using hierarchical Bayesian regression models with weakly informative priors. We will present the full posterior distributions of relative (risk ratios and ratios of means) and absolute differences (risk differences and mean differences) in each subgroup. DISCUSSION: This study will provide data on the effects of heterogeneity in treatment intensity while accounting for patient characteristics in critically ill adult patients with septic shock. REGISTRATIONS: The European Clinical Trials Database (EudraCT): 2018-000404-42, ClinicalTrials. gov: NCT03668236.

Early Postoperative Complications of Robotic-assisted Versus Minimally Invasive Mitral Valve Surgery: A Propensity Score-matched Analysis.

OBJECTIVE: The current work was designed to evaluate whether robotic-assisted mitral valve surgery is associated with a different incidence of early postoperative complications compared with the traditional minimally invasive approach. DESIGN: A retrospective monocentric cohort study was conducted. SETTING: The study was performed in an academic hospital. PARTICIPANTS: A total of 375 patients who underwent standard thoracoscopic minimally invasive mitral valve surgery and robotic-assisted mitral valve surgery between April 2014 and November 2022 were enrolled. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: After adjustment using propensity score analysis, 98 patients from each group were identified. Patients who underwent robotic surgery presented a similar rate of early complications to patients undergoing minimally invasive surgery. Nevertheless, they showed shorter intensive care unit and postoperative hospital stays. Finally, patients undergoing robotic-assisted surgery were more frequently discharged home. CONCLUSIONS: This study identified a similar incidence of early complications in robotic-assisted mitral valve surgery compared with minimally invasive mitral valve surgery; conversely, patients receiving robotic-assisted surgery were discharged earlier, and more frequently discharged home.

Transpulmonary thermodilution.

PURPOSE OF REVIEW: The purpose of this article is to systematically review and critically assess the existing data regarding the use of transpulmonary thermodilution (TPTD), by providing a detailed description of technical aspects of TPTD techniques, appraising the use of TPTD-derived parameters in specific clinical settings, and exploring the limits of this technique. RECENT FINDINGS: The aim of hemodynamic monitoring is to optimize cardiac output ( CO ) and therefore improve oxygen delivery to the tissues. Hemodynamic monitoring plays a fundamental role in the management of acutely ill patients. TPTD is a reliable, multiparametric, advanced cardiopulmonary monitoring technique providing not only hemodynamic parameters related to cardiac function, but also to the redistribution of the extravascular water in the thorax. The hemodynamic monitors available in the market usually couple the intermittent measurement of the CO by TPTD with the arterial pulse contour analysis, offering automatic calibration of continuous CO and an accurate assessment of cardiac preload and fluid responsiveness. SUMMARY: The TPTD is an invasive but well tolerated, multiparametric, advanced cardiopulmonary monitoring technique, allowing a comprehensive assessment of cardiopulmonary condition. Beyond the CO estimation, TPTD provides several indices that help answering questions that clinicians ask themselves during hemodynamic management. TPTD-guided algorithm obtained by pulse contour analysis may be useful to optimize fluid resuscitation by titrating fluid therapy according to functional hemodynamic monitoring and to define safety criteria to avoid fluid overload by following the changes in the extravascular lung water (EVLW) and pulmonary vascular permeability index (PVPI).

Diabetes mellitus is associated with 90-day mortality in old critically ill COVID-19 patients: a multicenter prospective observational cohort study.

BACKGROUND: Several studies have found an association between diabetes mellitus, disease severity and outcome in COVID-19 patients. Old critically ill patients are particularly at risk. This study aimed to investigate the impact of diabetes mellitus on 90-day mortality in a high-risk cohort of critically ill patients over 70 years of age. METHODS: This multicentre international prospective cohort study was performed in 151 ICUs across 26 countries. We included patients ≥ 70 years of age with a confirmed SARS-CoV-2 infection admitted to the intensive care unit from 19th March 2020 through 15th July 2021. Patients were categorized into two groups according to the presence of diabetes mellitus. Primary outcome was 90-day mortality. Kaplan-Meier overall survival curves until day 90 were analysed and compared using the log-rank test. Mixed-effect Weibull regression models were computed to investigate the influence of diabetes mellitus on 90-day mortality. RESULTS: This study included 3420 patients with a median age of 76 years were included. Among these, 37.3% (n = 1277) had a history of diabetes mellitus. Patients with diabetes showed higher rates of frailty (32% vs. 18%) and several comorbidities including chronic heart failure (20% vs. 11%), hypertension (79% vs. 59%) and chronic kidney disease (25% vs. 11%), but not of pulmonary comorbidities (22% vs. 22%). The 90-day mortality was significantly higher in patients with diabetes than those without diabetes (64% vs. 56%, p < 0.001). The association of diabetes and 90-day mortality remained significant (HR 1.18 [1.06-1.31], p = 0.003) after adjustment for age, sex, SOFA-score and other comorbidities in a Weibull regression analysis. CONCLUSION: Diabetes mellitus was a relevant risk factor for 90-day mortality in old critically ill patients with COVID-19. STUDY REGISTRATION: NCT04321265, registered March 19th, 2020.

Interventions to promote cost-effectiveness in adult intensive care units: consensus statement and considerations for best practice from a multidisciplinary and multinational eDelphi study.

BACKGROUND: There is limited evidence to guide interventions that promote cost-effectiveness in adult intensive care units (ICU). The aim of this consensus statement is to identify globally applicable interventions for best ICU practice and provide guidance for judicious use of resources. METHODS: A three-round modified online Delphi process, using a web-based platform, sought consensus from 61 multidisciplinary ICU experts (physicians, nurses, allied health, administrators) from 21 countries. Round 1 was qualitative to ascertain opinions on cost-effectiveness criteria based on four key domains of high-value healthcare (foundational elements; infrastructure fundamentals; care delivery priorities; reliability and feedback). Round 2 was qualitative and quantitative, while round 3 was quantitative to reiterate and establish criteria. Both rounds 2 and 3 utilized a five-point Likert scale for voting. Consensus was considered when > 70% of the experts voted for a proposed intervention. Thereafter, the steering committee endorsed interventions that were identified as 'critical' by more than 50% of steering committee members. These interventions and experts' comments were summarized as final considerations for best practice. RESULTS: At the conclusion of round 3, consensus was obtained on 50 best practice considerations for cost-effectiveness in adult ICU. Finally, the steering committee endorsed 9 'critical' best practice considerations. This included adoption of a multidisciplinary ICU model of care, focus on staff training and competency assessment, ongoing quality audits, thus ensuring high quality of critical care services whether within or outside the four walls of ICUs, implementation of a dynamic staff roster, multidisciplinary approach to implementing end-of-life care, early mobilization and promoting international consensus efforts on the Green ICU concept. CONCLUSIONS: This Delphi study with international experts resulted in 9 consensus statements and best practice considerations promoting cost-effectiveness in adult ICUs. Stakeholders (government bodies, professional societies) must lead the efforts to identify locally applicable specifics while working within these best practice considerations with the available resources.

Reliability of pulse pressure and stroke volume variation in assessing fluid responsiveness in the operating room: a metanalysis and a metaregression.

BACKGROUND: Pulse pressure and stroke volume variation (PPV and SVV) have been widely used in surgical patients as predictors of fluid challenge (FC) response. Several factors may affect the reliability of these indices in predicting fluid responsiveness, such as the position of the patient, the use of laparoscopy and the opening of the abdomen or the chest, combined FC characteristics, the tidal volume (Vt) and the type of anesthesia. METHODS: Systematic review and metanalysis of PPV and SVV use in surgical adult patients. The QUADAS-2 scale was used to assess the risk of bias of included studies. We adopted a metanalysis pooling of aggregate data from 5 subgroups of studies with random effects models using the common-effect inverse variance model. The area under the curve (AUC) of pooled receiving operating characteristics (ROC) curves was reported. A metaregression was performed using FC type, volume, and rate as independent variables. RESULTS: We selected 59 studies enrolling 2,947 patients, with a median of fluid responders of 55% (46-63). The pooled AUC for the PPV was 0.77 (0.73-0.80), with a mean threshold of 10.8 (10.6-11.0). The pooled AUC for the SVV was 0.76 (0.72-0.80), with a mean threshold of 12.1 (11.6-12.7); 19 studies (32.2%) reported the grey zone of PPV or SVV, with a median of 56% (40-62) and 57% (46-83) of patients included, respectively. In the different subgroups, the AUC and the best thresholds ranged from 0.69 and 0.81 and from 6.9 to 11.5% for the PPV, and from 0.73 to 0.79 and 9.9 to 10.8% for the SVV. A high Vt and the choice of colloids positively impacted on PPV performance, especially among patients with closed chest and abdomen, or in prone position. CONCLUSION: The overall performance of PPV and SVV in operating room in predicting fluid responsiveness is moderate, ranging close to an AUC of 0.80 only some subgroups of surgical patients. The grey zone of these dynamic indices is wide and should be carefully considered during the assessment of fluid responsiveness. A high Vt and the choice of colloids for the FC are factors potentially influencing PPV reliability. TRIAL REGISTRATION: PROSPERO (CRD42022379120), December 2022. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=379120.

Albumin administration in septic shock-Protocol for post-hoc analyses of data from a multicentre RCT.

BACKGROUND: Intravenous (IV) albumin is suggested for patients with septic shock who have received large amounts of IV crystalloids; a conditional recommendation based on moderate certainty of evidence. Clinical variation in the administration of IV albumin in septic shock may exist according to patient characteristics and location. METHODS: This is a protocol and statistical analysis plan for a post-hoc secondary study of the Conservative versus Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care (CLASSIC) RCT of 1554 adult ICU patients with septic shock. We will assess if specific baseline characteristics or trial site are associated with the administration of IV albumin during ICU stay using Cox models with competing events. All models will be adjusted for the treatment allocation in CLASSIC (restrictive vs. standard IV fluid), and all analyses will consider competing events (death, ICU discharge and loss-to-follow-up). We will present results as hazard ratios with 95% confidence intervals and p-values for the associations of baseline characteristics or site with IV albumin administration. Between-group differences (interactions) will be assessed using p-values from likelihood ratio tests. All results will be considered exploratory only. DISCUSSION: This secondary study of the CLASSIC RCT may yield important insight into potential practice variation in the administration of albumin in septic shock.

Fitbit Data to Assess Functional Capacity in Patients Before Elective Surgery: Pilot Prospective Observational Study.

BACKGROUND: Preoperative assessment is crucial to prevent the risk of complications of surgical operations and is usually focused on functional capacity. The increasing availability of wearable devices (smartwatches, trackers, rings, etc) can provide less intrusive assessment methods, reduce costs, and improve accuracy. OBJECTIVE: The aim of this study was to present and evaluate the possibility of using commercial smartwatch data, such as those retrieved from the Fitbit Inspire 2 device, to assess functional capacity before elective surgery and correlate such data with the current gold standard measure, the 6-Minute Walk Test (6MWT) distance. METHODS: During the hospital visit, patients were evaluated in terms of functional capacity using the 6MWT. Patients were asked to wear the Fitbit Inspire 2 for 7 days (with flexibility of -2 to +2 days) after the hospital visit, before their surgical operation. Resting heart rate and daily steps data were retrieved directly from the smartwatch. Feature engineering techniques allowed the extraction of heart rate over steps (HROS) and a modified version of Non-Exercise Testing Cardiorespiratory Fitness. All measures were correlated with 6MWT. RESULTS: In total, 31 patients were enrolled in the study (n=22, 71% men; n=9, 29% women; mean age 76.06, SD 4.75 years). Data were collected between June 2021 and May 2022. The parameter that correlated best with the 6MWT was the Non-Exercise Testing Cardiorespiratory Fitness index (r=0.68; P<.001). The average resting heart rate over the whole acquisition period for each participant had r=-0.39 (P=.03), even if some patients did not wear the device at night. The correlation of the 6MWT distance with the HROS evaluated at 1% quantile was significant, with Pearson coefficient of -0.39 (P=.04). Fitbit step count had a fair correlation of 0.59 with 6MWT (P<.001). CONCLUSIONS: Our study is a promising starting point for the adoption of wearable technology in the evaluation of functional capacity of patients, which was strongly correlated with the gold standard. The study also identified limitations in the availability of metrics, variability of devices, accuracy and quality of data, and accessibility as crucial areas of focus for future studies.

Cardiac dysfunction in patients affected by subarachnoid haemorrhage affects in-hospital mortality: A systematic review and metanalysis.

BACKGROUND: Subarachnoid haemorrhage (SAH) is a life-threatening condition with associated brain damage. Moreover, SAH is associated with a massive release of catecholamines, which may promote cardiac injury and dysfunction, possibly leading to haemodynamic instability, which in turn may influence a patient's outcome. OBJECTIVES: To study the prevalence of cardiac dysfunction (as assessed by echocardiography) in patients with SAH and its effect on clinical outcomes. DESIGN: Systematic review of observational studies. DATA SOURCES: We performed a systematic search over the last 20 years on MEDLINE and EMBASE databases. ELIGIBILITY CRITERIA: Studies reporting echocardiography findings in adult patients with SAH admitted to intensive care. Primary outcomes were in-hospital mortality and poor neurological outcome according to the presence or absence of cardiac dysfunction. RESULTS: We included a total of 23 studies (4 retrospective) enrolling 3511 patients. The cumulative frequency of cardiac dysfunction was 21% (725 patients), reported as regional wall motion abnormality in the vast majority of studies (63%). Due to the heterogeneity of clinical outcome data reporting, a quantitative analysis was carried out only for in-hospital mortality. Cardiac dysfunction was associated with a higher in-hospital mortality [odds ratio 2.69 (1.64 to 4.41); P  < 0.001; I2 = 63%]. The GRADE of evidence assessment resulted in very low certainty of evidence. CONCLUSION: About one in five patients with SAH develops cardiac dysfunction, which seems to be associated with higher in-hospital mortality. The consistency of cardiac and neurological data reporting is lacking, reducing the comparability of the studies in this field.

Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis: The MERCY Randomized Clinical Trial.

Importance: Meropenem is a widely prescribed ß-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes. Objective: To determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis. Design, Setting, and Participants: A double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022. Interventions: Patients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304). Main Outcomes and Measures: The primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events. Results: All 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients). Conclusions and Relevance: In critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. Trial Registration: ClinicalTrials.gov Identifier: NCT03452839.