Fluid balance neutralization secured by hemodynamic monitoring versus protocolized standard of care in critically ill patients requiring continuous renal replacement therapy: study protocol of the GO NEUTRAL randomized controlled trial.

BACKGROUND: Fluid overload is associated with worse outcome in critically ill patients requiring continuous renal replacement therapy (CRRT). Net ultrafiltration (UFNET) allows precise control of the fluid removal but is frequently ceased due to hemodynamic instability episodes. However, approximately 50% of the hemodynamic instability episodes in ICU patients treated with CRRT are not associated with preload dependence (i.e., are not related to a decrease in cardiac preload), suggesting that volume removal is not responsible for these episodes of hemodynamic impairment. The use of advanced hemodynamic monitoring, comprising continuous cardiac output monitoring to repeatedly assess preload dependency, could allow securing UFNET to allow fluid balance control and prevent fluid overload. METHODS: The GO NEUTRAL trial is a multicenter, open-labeled, randomized, controlled, superiority trial with parallel groups and balanced randomization with a 1:1 ratio. The trial will enroll adult patients with acute circulatory failure treated with vasopressors and severe acute kidney injury requiring CRRT who already have been equipped with a continuous cardiac output monitoring device. After informed consent, patients will be randomized into two groups. The control group will receive protocolized fluid removal with an UFNET rate set to 0-25 ml h-1 between inclusion and H72 of inclusion. The intervention group will be treated with an UFNET rate set on the CRRT of at least 100 ml h-1 between inclusion and H72 of inclusion if hemodynamically tolerated based on a protocolized hemodynamic protocol aiming to adjust UFNET based on cardiac output, arterial lactate concentration, and preload dependence assessment by postural maneuvers, performed regularly during nursing rounds, and in case of a hemodynamic instability episode. The primary outcome of the study will be the cumulative fluid balance between inclusion and H72 of inclusion. Randomization will be generated using random block sizes and stratified based on fluid overload status at inclusion. The main outcome will be analyzed in the modified intention-to-treat population, defined as all alive patients at H72 of inclusion, based on their initial allocation group. DISCUSSION: We present in the present protocol all study procedures in regard to the achievement of the GO NEUTRAL trial, to prevent biased analysis of trial outcomes and improve the transparency of the trial result report. Enrollment of patients in the GO NEUTRAL trial has started on June 31, 2021, and is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov NCT04801784. Registered on March 12, 2021, before the start of inclusion.

ACE2: a key modulator of the renin-angiotensin system and pregnancy.

Angiotensin-converting enzyme 2 (ACE2) is a membrane-bound protein containing 805 amino acids. ACE2 shows approximately 42% sequence similarity to somatic ACE but has different biochemical activities. The key role of ACE2 is to catalyze the vasoconstrictor peptide angiotensin (ANG) II to Ang-(1-7), thus regulating the two major counterbalancing pathways of the renin-angiotensin system (RAS). In this way, ACE2 plays a protective role in end-organ damage by protecting tissues from the proinflammatory actions of ANG II. The circulating RAS is activated in normal pregnancy and is essential for maintaining fluid and electrolyte homeostasis and blood pressure. Renin-angiotensin systems are also found in the conceptus. In this review, we summarize the current knowledge on the regulation and function of circulating and uteroplacental ACE2 in uncomplicated and complicated pregnancies, including those affected by preeclampsia and fetal growth restriction. Since ACE2 is the receptor for SARS-CoV-2, and COVID-19 in pregnancy is associated with more severe disease and increased risk of abnormal pregnancy outcomes, we also discuss the role of ACE2 in mediating some of these adverse consequences. We propose that dysregulation of ACE2 plays a critical role in the development of preeclampsia, fetal growth restriction, and COVID-19-associated pregnancy pathologies and suggest that human recombinant soluble ACE2 could be a novel therapeutic to treat and/or prevent these pregnancy complications.

The Beverage Hydration Index: Influence of Electrolytes, Carbohydrate and Protein.

The beverage hydration index (BHI) facilitates a comparison of relative hydration properties of beverages using water as the standard. The additive effects of electrolytes, carbohydrate, and protein on rehydration were assessed using BHI. Nineteen healthy young adults completed four test sessions in randomized order: deionized water (W), electrolytes only (E), carbohydrate-electrolytes (C + E), and 2 g/L dipeptide (alanyl-glutamine)-electrolytes (AG + E). One liter of beverage was consumed, after which urine and body mass were obtained every 60 min through 240 min. Compared to W, BHI was higher (p = 0.007) for C + E (1.15 ± 0.17) after 120 min and for AG + E (p = 0.021) at 240 min (1.15 ± 0.20). BHI did not differ (p > 0.05) among E, C + E, or AG + E; however, E contributed the greatest absolute net effect (>12%) on BHI relative to W. Net fluid balance was lower for W (p = 0.048) compared to C + E and AG + E after 120 min. AG + E and E elicited higher (p < 0.001) overall urine osmolality vs. W. W also elicited greater reports of stomach bloating (p = 0.02) compared to AG + E and C + E. The addition of electrolytes alone (in the range of sports drinks) did not consistently improve BHI versus water; however, the combination with carbohydrate or dipeptides increased fluid retention, although this occurred earlier for the sports drink than the dipeptide beverage. Electrolyte content appears to make the largest contribution in hydration properties of beverages for young adults when consumed at rest.

Education and training as key drivers for improving the quality of fluid balance charts: findings from a quality improvement project.

Reviewing fluid balance charts is a simple and effective method of assessing and monitoring the hydration status of patients. Several articles report that these charts are often either inaccurately or incompletely filled thereby limiting their usefulness in clinical practice. We had a similar experience in our practice at Kettering General Hospital and conducted a quality improvement project with a goal to increase the number of charts that were completely and accurately filled by a minimum of 50% in a 1-month period and to reassess the sustainability of this improvement after 6 months. Data from baseline measurements showed that only 25% of the charts in the ward had accurate measurements, 20% had correct daily totals and 14% had complete records of all intakes and losses. We collected feedback from nursing staff in the ward on what challenges they faced in using these charts and how best to support them. Corroborated by evidence from the literature, we discovered that inadequate training was a major factor responsible for the poor quality of documentation in these charts. Using simultaneous plan-do-study-act cycles, we designed and delivered personalised teaching on fluid balance chart documentation to the nursing staff. Subsequent data showed remarkable improvements in all the parameters we assessed. For instance, the proportion of charts with accurate measurements increased by 55% and those with complete entries by 122%. Unfortunately, we were unable to demonstrate sustainability of these improvements as our second set of data collection coincided with the SARS-CoV-2 outbreak. In this project, we were able to demonstrate that simple and cost-efficient measures such as adequate training of nursing staff could remarkably improve the quality of fluid balance charts used in our hospitals. We suggest that this training should be included as part of the regular competency assessments for nurses and other healthcare staff.

Calculated plasma osmolality at hospital admission correlates well with eGFR and D-Dimer, a simple outcome predictor and guiding tool for management of severe COVID-19 patients.

AIMS: To evaluate calculated total plasma osmolality as a marker of outcome prediction, fluid and metabolic balance, thrombotic risk in severe COVID-19 patients. METHODS: Retrospective data of RT-PCR confirmed hospitalized severe COVID-19 patients (total: n = 175 patients, including diabetic subset: n = 102) were analyzed. Clinically applicable cut-offs were derived using receiver operating characteristic (ROC) curve analysis for calculated total osmolality, eGFR, and D-dimer, and their correlations were studied. RESULTS: Among 175 severe COVID-19 patients, a significant association with mortality was seen with respect to calculated total osmolality (p < 0.001), eGFR (p < 0.001), and D-dimer (p < 0.001). In the total cohort, applicable cut-offs based on ROC curve in predicting outcome were, for total osmolality 299 mosm/kg (area under the curve (AUC)-0.773, odds ratio (OR)-1.09), eGFR 61.5 ml/min/m2 (AUC-0.789, OR-0.96), D-dimer 5.13 (AUC-0.814, OR-2.65) respectively. In diabetic subset, the cut-offs for total osmolality were 298 mosm/kg (AUC-0.794, OR-1.12), eGFR 44.9 ml/min/m2 (AUC-0.774, OR-0.96) and D-dimer 1.59 (AUC-0.769, OR-1.52) respectively. CONCLUSIONS: Applicable cut-offs for calculated total plasma osmolality, eGFR, and D-dimer predicts clinical outcome in severe COVID-19 with and without diabetes. Correlation studies validated calculated total osmolality as a marker of the combined effect of fluid and metabolic imbalance, compromised renal function and hypercoagulability.

Volume Balance in Chronic Kidney Disease: Evaluation Methodologies and Innovation Opportunities.

BACKGROUND: Patients affected by chronic kidney disease are at a risk of cardiovascular morbidity and mortality. Body fluids unbalance is one of the main characteristics of this condition, as fluid overload is highly prevalent in patients affected by the cardiorenal syndrome. SUMMARY: We describe the state of the art and new insights into body volume evaluation. The mechanisms behind fluid balance are often complex, mainly because of the interplay of multiple regulatory systems. Consequently, its management may be challenging in clinical practice and even more so out-of-hospital. Availability of novel technologies offer new opportunities to improve the quality of care and patients' outcome. Development and validation of new technologies could provide new tools to reduce costs for the healthcare system, promote personalized medicine, and boost home care. Due to the current COVID-19 pandemic, a proper monitoring of chronic patients suffering from fluid unbalances is extremely relevant. Key Message: We discuss the main mechanisms responsible for fluid overload in different clinical contexts, including hemodialysis, peritoneal dialysis, and heart failure, emphasizing the potential impact provided by the implementation of the new technologies.

Symptomatic sinus bradycardia due to electrolyte imbalances in syndrome of inappropriate antidiuretic hormone (SIADH) related covid-19: a case report.

BACKGROUND: Coronavirus Disease-2019 (COVID-19) has been declared a global pandemic since March 11th, 2020. Despite emerging reports and literature covering a broad spectrum of COVID-19 clinical manifestations, facets of COVID-19 have not been fully elucidated. To the authors' concern, sinus bradycardia as a manifestation of COVID-19-induced syndrome of inappropriate antidiuretic hormone (SIADH) has never been reported before. CASE PRESENTATION: In this paper, we report a case of a 59-year-old male patient with confirmed COVID-19 initially presented with presyncope. Further investigations reveal sinus bradycardia related to COVID-19-induced SIADH. This case highlights the possibility of immuno-neuroendocrino-cardiovascular crosstalk resulting in an atypical manifestation of COVID-19: near syncope due to sinus bradycardia. CONCLUSIONS: Another possible cause of sinus bradycardia in COVID-19 is electrolyte imbalance due to COVID-19-related SIADH.

Clinical characteristics and outcome of critically ill COVID-19 patients with acute kidney injury: a single centre cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common manifestation among patients critically ill with SARS-CoV-2 infection (Coronavirus 2019) and is associated with significant morbidity and mortality. The pathophysiology of renal failure in this context is not fully understood, but likely to be multifactorial. The intensive care unit outcomes of patients following COVID-19 acute critical illness with associated AKI have not been fully explored. We conducted a cohort study to investigate the risk factors for acute kidney injury in patients admitted to and intensive care unit with COVID-19, its incidence and associated outcomes. METHODS: We reviewed the medical records of all patients admitted to our adult intensive care unit suffering from SARS-CoV-2 infection from 14th March 2020 until 12th May 2020. Acute kidney injury was defined using the Kidney Disease Improving Global Outcome (KDIGO) criteria. The outcome analysis was assessed up to date as 3rd of September 2020. RESULTS: A total of 81 patients admitted during this period. All patients had acute hypoxic respiratory failure and needed either noninvasive or invasive mechanical ventilatory support. Thirty-six patients (44%) had evidence of AKI (Stage I-33%, Stage II-22%, Renal Replacement Therapy (RRT)-44%). All patients with AKI stage III had RRT. Age, diabetes mellitus, immunosuppression, lymphopenia, high D-Dimer levels, increased APACHE II and SOFA scores, invasive mechanical ventilation and use of inotropic or vasopressor support were significantly associated with AKI. The peak AKI was at day 4 and mean duration of RRT was 12.5 days. The mortality was 25% for the AKI group compared to 6.7% in those without AKI. Among those received RRT and survived their illness, the renal function recovery is complete and back to baseline in all patients. CONCLUSION: Acute kidney injury and renal replacement therapy is common in critically ill patients presenting with COVID-19. It is associated with increased severity of illness on admission to ICU, increased mortality and prolonged ICU and hospital length of stay. Recovery of renal function was complete in all survived patients.

SARS-CoV-2 infection in an infant with severe dilated cardiomyopathy.

A four- and a half-month-old girl with severe dilated cardiomyopathy due to neonatal enterovirus myocarditis, treated with diuretics and milrinone for the past 4 months, was infected with SARS-CoV-2. The disease course was characterised by high fever and gastrointestinal symptoms. Cardiac function, as measured by echocardiography, remained stable. The treatment focused on maintaining a normal heart rate and a stable fluid balance. In children with severe underlying cardiac disease, even a mild SARS-CoV-2 infection can require close monitoring and compound treatment.

Slow Recovery from Critical Coronavirus Disease 2019 Pneumonia in an Immunosuppressed Renal Transplant Recipient with Early Acute Cardiorenal Syndrome.

With the global spread of SARS-Cov-2 infections, increasing numbers of COVID-19 cases have been reported in transplant recipients. However, reports are lacking concerning the treatment and prognosis of COVID-19 pneumonia in renal transplant recipients with acute cardiorenal syndrome. We report here the complete clinical course of a renal transplant recipient with critical COVID-19 pneumonia. In the early phase of SARS-Cov-2 infection, the patient exhibited extensive lung lesions and significant acute kidney and heart injuries, which required treatment in the ICU. After correcting the arrhythmia and heart failure, the patient recovered quickly from the acute kidney injury with a treatment of intensive diuresis and strict control of fluid intake. Without cessation of oral immunosuppressive agents, the patient presented a delayed and low antibody response against SARS-Cov-2 and reappeared positive for the virus twice after being discharged. Nevertheless, the patient's pneumonia continued to improve and he fully recovered in 69 days. This effectively treated case may be meaningful and referable for the treatment of COVID-19 pneumonia in other transplant recipients with acute cardiorenal syndrome.

Impact of Circulating SARS-CoV-2 Mutant G614 on the COVID-19 Pandemic.

Coronavirus family has caused several human illnesses, the latest caused by SARS-CoV-2, has led to COVID-19 pandemic posing serious threat to global health. A SARS-CoV-2 variant encoding a D614G mutation in the viral spike (S) protein has now become the most prevalent form of the virus worldwide, suggesting a fitness advantage for the mutant. The G614 variant is associated with higher upper respiratory tract viral load, higher infectivity, increased total S protein incorporation into the virion, reduced S1 shedding and a conformational change leading to a more ACE2- binding and fusion- competent state. However, it does not seem to be correlated to increased disease severity or escape neutralizing antibodies.

COVID-19 in patients with heart failure: the new and the old epidemic.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread in nearly 200 countries in less than 4 months since its first identification; accordingly, the coronavirus disease 2019 (COVID 2019) has affirmed itself as a clinical challenge. The prevalence of pre-existing cardiovascular diseases in patients with COVID19 is high and this dreadful combination dictates poor prognosis along with the higher risk of intensive care mortality. In the setting of chronic heart failure, SARS-CoV-2 can be responsible for myocardial injury and acute decompensation through various mechanisms. Given the clinical and epidemiological complexity of COVID-19, patiens with heart failure may require particular care since the viral infection has been identified, considering an adequate re-evaluation of medical therapy and a careful monitoring during ventilation.

Acute Kidney Injury in Patients with the Coronavirus Disease 2019: A Multicenter Study.

INTRODUCTION: Severe acute respiratory viral infections are frequency accompanied by multiple organ dysfunction, including acute kidney injury (AKI). In December 2019, the coronavirus disease 2019 (COVID-19) outbreak began in Wuhan, Hubei Province, China, and rapidly spread worldwide. While diffuse alveolar damage and acute respiratory failure are the main features of COVID-19, other organs may be involved, and the incidence of AKI is not well described. We assessed the incidence and clinical characteristics of AKI in patients with laboratory-confirmed COVID-19 and its effects on clinical outcomes. METHODS: We conducted a multicenter, retrospective, observational study of patients with COVID-19 admitted to two general hospitals in Wuhan from 5 January 2020 to 21 March 2020. Demographic data and information on organ dysfunction were collected daily. AKI was defined according to the KDIGO clinical practice guidelines. Early and late AKI were defined as AKI occurring within 72 h after admission or after 72 h, respectively. RESULTS: Of the 116 patients, AKI developed in 21 (18.1%) patients. Among them, early and late AKI were found in 13 (11.2%) and 8 (6.9%) patients, respectively. Compared with patients without AKI, patients with AKI had more severe organ dysfunction, as indicated by a higher level of disease severity status, higher sequential organ failure assessment (SOFA) score on admission, an increased prevalence of shock, and a higher level of respiratory support. Patients with AKI had a higher SOFA score on admission (4.5 ± 2.1 vs. 2.8 ± 1.4, OR 1.498, 95% CI 1.047-2.143 ) and greater hospital mortality (57.1% vs. 12.6%, OR 3.998, 95% CI 1.088-14.613) than patients without AKI in both the univariate and multivariate analyses. Patients with late AKI, but not those with early AKI, had a significantly prolonged length of stay (19.6 vs. 9.6 days, p = 0.015). CONCLUSION: Our findings show that admission SOFA score was an independent risk factor for AKI in COVID-19 patients, and patients with AKI had higher in-hospital mortality. Moreover, AKI development after 72 h of admission was related to prolonged hospitalization time.

Biochemical biomarkers alterations in Coronavirus Disease 2019 (COVID-19).

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory disease, which can evolve into multi-organ failure (MOF), leading to death. Several biochemical alterations have been described in COVID-19 patients. To date, many biomarkers reflecting the main pathophysiological characteristics of the disease have been identified and associated with the risk of developing severe disease. Lymphopenia represents the hallmark of the disease, and it can be detected since the early stage of infection. Increased levels of several inflammatory biomarkers, including c-reactive protein, have been found in COVID-19 patients and associated with an increased risk of severe disease, which is characterised by the so-called "cytokine storm". Also, the increase of cardiac and liver dysfunction biomarkers has been associated with poor outcome. In this review, we provide an overview of the main biochemical characteristics of COVID-19 and the associated biomarkers alterations.

Electrolyte imbalances in patients with severe coronavirus disease 2019 (COVID-19).

BACKGROUND: Early studies have reported various electrolyte abnormalities at admission in patients who progress to the severe form of coronavirus disease 2019 (COVID-19). As electrolyte imbalance may not only impact patient care, but provide insight into the pathophysiology of COVID-19, we aimed to analyse all early data reported on electrolytes in COVID-19 patients with and without severe form. METHODS: An electronic search of Medline (PubMed interface), Scopus and Web of Science was performed for articles comparing electrolytes (sodium, potassium, chloride and calcium) between COVID-19 patients with and without severe disease. A pooled analysis was performed to estimate the weighted mean difference (WMD) with 95% confidence interval. RESULTS: Five studies with a total sample size of 1415 COVID-19 patients. Sodium was significantly lower in patients with severe COVID-19 (WMD: -0.91 mmol/L [95% CI: -1.33 to -0.50 mmol/L]). Similarly, potassium was also significantly lower in COVID-19 patients with severe disease (WMD: -0.12 mmol/L [95% CI: -0.18 to -0.07 mmol/L], I2=33%). For chloride, no statistical differences were observed between patients with severe and non-severe COVID-19 (WMD: 0.30 mmol/L [95% CI: -0.41 to 1.01 mmol/L]). For calcium, a statistically significant lower concentration was noted in patients with severe COVID-19 (WMD: -0.20 mmol/L [95% CI: -0.25 to -0.20 mmol/L]). CONCLUSIONS: This pooled analysis confirms that COVID-19 severity is associated with lower serum concentrations of sodium, potassium and calcium. We recommend electrolytes be measured at initial presentation and serially monitored during hospitalization in order to establish timely and appropriate corrective actions.

Short Report - Medical nutrition therapy for critically ill patients with COVID-19.

No Abstract Available.