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.

Consistency of data reporting in fluid responsiveness studies in the critically ill setting: the CODEFIRE consensus from the Cardiovascular Dynamic section of the European Society of Intensive Care Medicine.

PURPOSE: To provide consensus recommendations regarding hemodynamic data reporting in studies investigating fluid responsiveness and fluid challenge (FC) use in the intensive care unit (ICU). METHODS: The Executive Committee of the European Society of Intensive Care Medicine (ESICM) commissioned and supervised the project. A panel of 18 international experts and a methodologist identified main domains and items from a systematic literature, plus 2 ancillary domains. A three-step Delphi process based on an iterative approach was used to obtain the final consensus. In the Delphi 1 and 2, the items were selected with strong (≥ 80% of votes) or week agreement (70-80% of votes), while the Delphi 3 generated recommended (≥ 90% of votes) or suggested (80-90% of votes) items (RI and SI, respectively). RESULTS: We identified 5 main domains initially including 117 items and the consensus finally resulted in 52 recommendations or suggestions: 18 RIs and 2 SIs statements were obtained for the domain "ICU admission", 11 RIs and 1 SI for the domain "mechanical ventilation", 5 RIs for the domain "reason for giving a FC", 8 RIs for the domain pre- and post-FC "hemodynamic data", and 7 RIs for the domain "pre-FC infused drugs". We had no consensus on the use of echocardiography, strong agreement regarding the volume (4 ml/kg) and the reference variable (cardiac output), while weak on administration rate (within 10 min) of FC in this setting. CONCLUSION: This consensus found 5 main domains and provided 52 recommendations for data reporting in studies investigating fluid responsiveness in ICU patients.

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.

Modulation of the capillary leakage by exogenous albumin in a rat model of endothelial glycocalyx damage.

BACKGROUND: Endothelial glycocalyx (EG) plays a crucial role in maintaining the plasma proteins within the intravascular space. OBJECTIVE: We studied whether exogenous albumin protects the EG in an experimental model of EG enzymatic damage in rats. METHODS: Rats were divided into three groups of 10 animals that received (1) Evans blue (2) Evans blue + hyaluronidase, or (3) Evans blue + hyaluronidase + 20% human albumin via the tail vein. Spectrophotometric analysis was performed 2 h later to quantify the leakage of Evans blue-labeled albumin into the heart, lungs, brain, kidneys, liver, small intestine, spleen, and skeletal muscle. RESULTS: Administration of hyaluronidase numerically increased the capillary leakage of Evans blue in all examined tissues. Co-administration of albumin decreased the leakage of albumin in all tissues except the heart. In the lungs, the ratio between the absorbance and dry organ weight decreased from 5.3 ± 2.4 to 1.7 ± 0.5 (mean ± SD) (P <  0.002), and in the liver, the absorbance decreased from 2.2 ± 0.7 to 1.5 ± 0.4 (P <  0.011). CONCLUSION: Exogenous albumin decreased the capillary leakage of albumin which was interpreted as a sign of maintained EG integrity.

Evaluation of the TraumaGuard Balloon-in-Balloon Catheter Design for Intra-Abdominal Pressure Monitoring: Insights from Pig and Human Cadaver Studies.

Introduction: Intra-abdominal pressure (IAP) monitoring is crucial for the detection and prevention of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS). In the 1970s, air-filled catheters (AFCs) for urodynamic studies were introduced as a solution to overcome the limitations of water-perfused catheters. Recent studies have shown that for correct IAP measurement with traditional AFC, the bladder needs to be primed with 25 mL of saline solution to allow pressure wave transmission to the transducer outside of the body, which limits continuous IAP monitoring. Methods: In this study, a novel triple balloon, air-filled TraumaGuard (TG) catheter system from Sentinel Medical Technologies (Jacksonville, FL, USA) with a unique balloon-in-balloon design was evaluated in a porcine and cadaver model of IAH via laparoscopy (IAPgold). Results: In total, 27 and 86 paired IAP measurements were performed in two pigs and one human cadaver, respectively. The mean IAPTG was 20.7 ± 10.7 mmHg compared to IAPgold of 20.3 ± 10.3 mmHg in the porcine study. In the cadaver investigation, the mean IAPTG was 15.6 ± 10.8 mmHg compared to IAPgold of 14.4 ± 10.4 mmHg. The correlation, concordance, bias, precision, limits of agreement, and percentage error were all in accordance with the WSACS (Abdominal Compartment Society) recommendations and guidelines for research. Conclusions: These findings support the use of the TG catheter for continuous IAP monitoring, providing early detection of elevated IAP, thus enabling the potential for prevention of IAH and ACS. Confirmation studies with the TraumaGuard system in critically ill patients are warranted to further validate these findings.

In Vitro Validation of a Novel Continuous Intra-Abdominal Pressure Measurement System (TraumaGuard).

Introduction: Intra-abdominal pressure (IAP) has been recognized as an important vital sign in critically ill patients. Due to the high prevalence and incidence of intra-abdominal hypertension in surgical (trauma, burns, cardiac) and medical (sepsis, liver cirrhosis, acute kidney injury) patients, continuous IAP (CIAP) monitoring has been proposed. This research was aimed at validating a new CIAP monitoring device, the TraumaGuard from Sentinel Medical Technologies, against the gold standard (height of a water column) in an in vitro setting and performing a comparative analysis among different CIAP measurement technologies (including two intra-gastric and two intra-bladder measurement devices). A technical and clinical guideline addressing the strengths and weaknesses of each device is provided as well. Methods: Five different CIAP measurement devices (two intra-gastric and three intra-vesical), including the former CiMON, Spiegelberg, Serenno, TraumaGuard, and Accuryn, were validated against the gold standard water column pressure in a bench-top abdominal phantom. The impacts of body temperature and bladder fill volume (for the intra-vesical methods) were evaluated for each system. Subsequently, 48 h of continuous monitoring (n = 2880) on top of intermittent IAP (n = 300) readings were captured for each device. Using Pearson's and Lin's correlations, concordance, and Bland and Altman analyses, the accuracy, precision, percentage error, correlation and concordance coefficients, bias, and limits of agreement were calculated for all the different devices. We also performed error grid analysis on the CIAP measurements to provide an overview of the involved risk level due to wrong IAP measurements and calculated the area under the curve and time above a certain IAP threshold. Lastly, the robustness of each system in tracking the dynamic variations of the raw IAP signal due to respirations and heartbeats was evaluated as well. Results: The TraumaGuard was the only technology able to measure the IAP with an empty artificial bladder. No important temperature dependency was observed for the investigated devices except for the Spiegelberg, which displayed higher IAP values when the temperature was increased, but this could be adjusted through recalibration. All the studied devices showed excellent ability for IAP monitoring, although the intra-vesical IAP measurements seem more reliable. In general, the TraumaGuard, Accuryn, and Serenno showed better accuracy compared to intra-gastric measurement devices. On average, biases of +0.71, +0.93, +0.29, +0.25, and -0.06 mm Hg were observed for the CiMON, Spiegelberg, Serenno, TraumaGuard, and Accuryn, respectively. All of the equipment showed percentage errors smaller than 25%. Regarding the correlation and concordance coefficients, the Serenno and TraumaGuard showed the best results (R2 = 0.98, p = 0.001, concordance coefficient of 99.5%). Error grid analysis based on the Abdominal Compartment Society guidelines showed a very low associated risk level of inappropriate treatment strategies due to erroneous IAP measurements. Regarding the dynamic tracings of the raw IAP signal, all the systems can track respiratory variations and derived parameters; however, the CiMON was slightly superior compared to the other technologies. Conclusions: According to the research guidelines of the Abdominal Compartment Society (WSACS), this in vitro study shows that the TraumaGuard can be used interchangeably with the gold standard for measuring continuous IAP, even in an empty artificial bladder. Confirmation studies with the TraumaGuard in animals and humans are warranted to further validate these findings.

Multidisciplinary expert panel report on fluid stewardship: perspectives and practice.

Although effective and appropriate fluid management is a critical aspect of quality care during hospitalization, the widespread adoption of consistent policies that ensure adequate fluid stewardship has been slow and heterogenous. Despite evidence-based guidelines on fluid management being available, clinical opinions continue to diverge on important aspects of care in this setting, and the consistency of guideline implementation is far from ideal. A multidisciplinary panel of leading practitioners and experts convened to discuss best practices for ongoing staff education, intravenous fluid therapy, new training technologies, and strategies to track the success of institutional fluid stewardship efforts. Fluid leads should be identified in every hospital to ensure consistency in fluid administration and monitoring. In this article, strategies to communicate the importance of effective fluid stewardship for the purposes of education, training, institutional support, and improvement of patient outcomes are reviewed and recommendations are summarized.

A survey of preferences for respiratory support in the intensive care unit for patients with acute hypoxaemic respiratory failure.

BACKGROUND: When caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians' preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers. METHODS: We distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice. RESULTS: The survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF. CONCLUSIONS: The responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.

Protection of the endothelium and endothelial glycocalyx by hydrogen against ischaemia-reperfusion injury in a porcine model of cardiac arrest.

BACKGROUND: Hydrogen is a potent antioxidant agent that can easily be administered by inhalation. The aim of the study was to evaluate whether hydrogen protects the endothelial glycocalyx layer after successful cardiopulmonary resuscitation (CPR). METHODS: Fourteen anesthetized pigs underwent CPR after induced ventricular fibrillation. During CPR and return of spontaneous circulation, 2% hydrogen gas was administered to seven pigs (hydrogen group) and seven constituted a control group. Biochemistry and sublingual microcirculation were assessed at baseline, during CPR, at the 15th, 30th, 60th, 120th minute. RESULTS: All seven subjects from the hydrogen group and six subjects in the control group were successfully resuscitated after 6-10 minutes. At baseline, there were no statistically significant differences in examined variables. After the CPR, blood pH, base excess, and lactate showed significantly smaller deterioration in the hydrogen group than in the control group. By contrast, plasma syndecan-1 and the measured variables obtained via sublingual microcirculation did not change after the CPR; and were virtually identical between the two groups. CONCLUSION: In pigs, hydrogen gas inhalation during CPR and post-resuscitation care was associated with less pronounced metabolic acidosis compared to controls. However, we could not find evidence of injury to the endothelium or glycocalyx in any studied groups.

Source control in emergency general surgery: WSES, GAIS, SIS-E, SIS-A guidelines.

Intra-abdominal infections (IAI) are among the most common global healthcare challenges and they are usually precipitated by disruption to the gastrointestinal (GI) tract. Their successful management typically requires intensive resource utilization, and despite the best therapies, morbidity and mortality remain high. One of the main issues required to appropriately treat IAI that differs from the other etiologies of sepsis is the frequent requirement to provide physical source control. Fortunately, dramatic advances have been made in this aspect of treatment. Historically, source control was left to surgeons only. With new technologies non-surgical less invasive interventional procedures have been introduced. Alternatively, in addition to formal surgery open abdomen techniques have long been proposed as aiding source control in severe intra-abdominal sepsis. It is ironic that while a lack or even delay regarding source control clearly associates with death, it is a concept that remains poorly described. For example, no conclusive definition of source control technique or even adequacy has been universally accepted. Practically, source control involves a complex definition encompassing several factors including the causative event, source of infection bacteria, local bacterial flora, patient condition, and his/her eventual comorbidities. With greater understanding of the systemic pathobiology of sepsis and the profound implications of the human microbiome, adequate source control is no longer only a surgical issue but one that requires a multidisciplinary, multimodality approach. Thus, while any breach in the GI tract must be controlled, source control should also attempt to control the generation and propagation of the systemic biomediators and dysbiotic influences on the microbiome that perpetuate multi-system organ failure and death. Given these increased complexities, the present paper represents the current opinions and recommendations for future research of the World Society of Emergency Surgery, of the Global Alliance for Infections in Surgery of Surgical Infection Society Europe and Surgical Infection Society America regarding the concepts and operational adequacy of source control in intra-abdominal infections.

Fluid management strategies and their interaction with mechanical ventilation: from experimental studies to clinical practice.

Patients on mechanical ventilation may receive intravenous fluids via restrictive or liberal fluid management. A clear and objective differentiation between restrictive and liberal fluid management strategies is lacking in the literature. The liberal approach has been described as involving fluid rates ranging from 1.2 to 12 times higher than the restrictive approach. A restrictive fluid management may lead to hypoperfusion and distal organ damage, and a liberal fluid strategy may result in endothelial shear stress and glycocalyx damage, cardiovascular complications, lung edema, and distal organ dysfunction. The association between fluid and mechanical ventilation strategies and how they interact toward ventilator-induced lung injury (VILI) could potentiate the damage. For instance, the combination of a liberal fluids and pressure-support ventilation, but not pressure control ventilation, may lead to further lung damage in experimental models of acute lung injury. Moreover, under liberal fluid management, the application of high positive end-expiratory pressure (PEEP) or an abrupt decrease in PEEP yielded higher endothelial cell damage in the lungs. Nevertheless, the translational aspects of these findings are scarce. The aim of this narrative review is to provide better understanding of the interaction between different fluid and ventilation strategies and how these interactions may affect lung and distal organs. The weaning phase of mechanical ventilation and the deresuscitation phase are not explored in this review.

Long-term effects of restriction of intravenous fluid in adult ICU patients with septic shock.

PURPOSE: To assess long-term outcomes of restrictive versus standard intravenous (IV) fluid therapy in adult intensive care unit (ICU) patients with septic shock included in the European Conservative versus Liberal Approach to Fluid Therapy in Septic Shock in Intensive Care (CLASSIC) trial. METHODS: We conducted the pre-planned analyses of mortality, health-related quality of life (HRQoL) using EuroQol (EQ)-5D-5L index values and EQ visual analogue scale (VAS), and cognitive function using Mini Montreal Cognitive Assessment (Mini MoCA) test at 1 year. Deceased patients were assigned numerical zero for HRQoL as a state equal to death and zero for cognitive function outcomes as worst possible score, and we used multiple imputation for missing data on HRQoL and cognitive function. RESULTS: Among 1554 randomized patients, we obtained 1-year data on mortality in 97.9% of patients, HRQoL in 91.3%, and cognitive function in 86.3%. One-year mortality was 385/746 (51.3%) in the restrictive-fluid group versus 383/767 (49.9%) in the standard-fluid group, absolute risk difference 1.5%-points [99% confidence interval (CI) - 4.8 to 7.8]. Mean differences were 0.00 (99% CI - 0.06 to 0.05) for EQ-5D-5L index values, - 0.65 for EQ VAS (- 5.40 to 4.08), and - 0.14 for Mini MoCA (- 1.59 to 1.14) for the restrictive-fluid group versus the standard-fluid group. The results for survivors only were similar in both groups. CONCLUSIONS: Among adult ICU patients with septic shock, restrictive versus standard IV fluid therapy resulted in similar survival, HRQoL, and cognitive function at 1 year, but clinically important differences could not be ruled out.

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.

Feasibility analysis of a novel non-invasive ultrasonographic method for the measurement of intra-abdominal pressure in the intensive care unit.

Increased intra-abdominal pressure (IAP) is an important vital sign in critically ill patients and has a negative impact on morbidity and mortality. This study aimed to validate a novel non-invasive ultrasonographic approach to IAP measurement against the gold standard intra-bladder pressure (IBP) method. We conducted a prospective observational study in an adult medical ICU of a university hospital. IAP measurements using ultrasonography by two independent operators, with different experience levels (experienced, IAPUS1; inexperienced, IAPUS2), were compared with the gold standard IBP method performed by a third blinded operator. For the ultrasonographic method, decremental external pressure was applied on the anterior abdominal wall using a bottle filled with decreasing volumes of water. Ultrasonography looked at peritoneal rebound upon brisk withdrawal of the external pressure. The loss of peritoneal rebound was identified as the point where IAP was equal to or above the applied external pressure. Twenty-one patients underwent 74 IAP readings (range 2-15 mmHg). The number of readings per patient was 3.5 ± 2.5, and the abdominal wall thickness was 24.6 ± 13.1 mm. Bland and Altman's analysis showed a bias (0.39 and 0.61 mmHg) and precision (1.38 and 1.51 mmHg) for the comparison of IAPUS1 and IAPUS2 and vs. IBP, respectively with small limits of agreement that were in line with the research guidelines of the Abdominal Compartment Society (WSACS). Our novel ultrasound-based IAP method displayed good correlation and agreement between IAP and IBP at levels up to 15 mmHg and is an excellent solution for quick decision-making in critically ill patients.

Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study.

Background: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population. Methods: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases. Findings: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism. Interpretation: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term. Funding: None.

Early detection of oliguric events in critically ill patients in the ICU with a novel continuous urine flow measurement device: results of an initial validation study.

OBJECTIVES: Urine output is used to evaluate fluid status and is an important marker for acute kidney injury (AKI). Our primary aim was to validate a new automatic urine output monitoring device by comparison to the current practice - the standard urometer. METHODS: We conducted a prospective observational study in three ICUs. Urine flow measurements by Serenno Medical Automatic urine output measuring device (Serenno Medical, Yokneam, Israel) were compared to standard urometer readings taken automatically at 5-minutes intervals by a camera, and to hourly urometer readings by the nurses, both over 1 to 7 days. Our primary outcome was the difference between urine flow assessed by the Serenno device and reference camera-derived measurements (Camera). Our secondary outcome was the difference between urine flow assessed by the Serenno device and hourly nursing assessments (Nurse), and detection of oliguria. RESULTS: Thirty-seven patients completed the study, with 1,306 h of recording and a median of 25 measurement hours per patient. Bland and Altman analysis comparing the study device to camera measurements demonstrated good agreement, with a bias of -0.4 ml/h and 95% confidence intervals ranging from - 28 to 27ml/h. Concordance was 92%. The correlation between Camera and hourly nursing assessment of urine output was distinctly worse with a bias of 7.2 ml and limits of agreement extending from - 75 to + 107 ml. Severe oliguria (urine output < 0.3 ml/kg/h) lasting 2 h or more was common and observed in 8 (21%) of patients. Among the severe oliguric events lasting more than 3 consecutive hours, 6 (41%) were not detected or documented by the nursing staff. There were no device-related complications. CONCLUSION: The Serenno Medical Automatic urine output measuring device required minimal supervision, little ICU nursing staff attention, and is sufficiently accurate and precise. In addition to providing continuous assessments of urine output, it was considerably more accurate than hourly nursing assessments.

Fluid Management for Critically Ill Patients with Acute Kidney Injury Receiving Kidney Replacement Therapy: An International Survey.

BACKGROUND: In critically ill patients receiving KRT, high ultrafiltration rates and persistent fluid accumulation are associated with adverse outcomes. The purpose of this international survey was to evaluate current practices and evidence gaps related to fluid removal with KRT in critically ill patients. METHODS: This was a multinational, web-based survey distributed by seven networks comprising nephrologists and intensivists. Physicians involved in the care of critically ill patients were invited to complete a 39-question survey about fluid management practices on KRT. The survey was distributed from September 2021 to December 2021. RESULTS: There were 757 respondents from 96 countries (response rate of 65%). Most respondents practiced adult medicine (89%) and worked in an academic center (69%). The majority (91%) reported aiming for a 0.5- to 2-L negative fluid balance per day when fluid removal is indicated, although there was important variability in what respondents considered a safe maximal target. Intensivists were more likely than nephrologists to use adjunct volume status assessment methods ( i.e. , ultrasound, hemodynamic markers, and intra-abdominal pressure), while nephrologists were more likely to deploy cointerventions aimed at improving tolerance to fluid removal ( i.e. , osmotic agents and low-temperature dialysate). There was a broad consensus that rapid decongestion should be prioritized when fluid accumulation is present, but the prevention of hypotension was also reported as a competing priority. A majority (77%) agreed that performing trials that compare fluid management strategies would be ethical and clinically relevant. CONCLUSIONS: We have identified multiple areas of variability in current practice of fluid management for patients receiving KRT. Most nephrologists and intensivists agreed that several knowledge gaps related to fluid removal strategies should be investigated in future randomized controlled trials.