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Patrick M Honoré,1 Rita Jacobs,1 Olivier Joannes-Boyau,2 Elisabeth De Waele,1 Jouke De Regt,1 Viola Van Gorp,1 Herbert D Spapen1 1ICU Department, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium; 2ICU Department, Haut Leveque University Hospital of Bordeaux, University of Bordeaux 2, Pessac, France Abstract: Emergency and critical care medicine have grown into robust self-supporting disciplines with an increasing demand for dedicated highly-skilled physicians. In the past, “core” specialists were asked to offer bedside advice in acute care wards. In the same regard, critical care medicine and nephrology have been fighting but finally emerged altogether with the concept of critical care nephrology almost 20 years ago. Indeed, polyvalence is no longer a valid option in modern critical care. Uniting forces between disciplines represents the only way to cope with the increasing complexity and cumulating knowledge in the critical care setting. For this reason, the wide array of upcoming acute care sub-specialities must be committed to unrestricted growth and development. This will require competent manpower, a well-designed technical framework, and sufficient financial support. The worldwide success of critical care nephrology proves the feasibility for this concept. Keywords: translational medicine, multidisciplinarity, acute medicine, CRRT, dialysis, critical care nephrology

R Kishen,1,2 Patrick M Honoré,3 R Jacobs,3 O Joannes-Boyau,4 E De Waele,3 J De Regt,3 V Van Gorp,3 W Boer,5 HD Spapen3 1Intensive Care Unit, Salford Royal Hospitals NHS Trust, Salford, Manchester, UK (formerly); 2Translational Medicine and Neurosciences, University of Manchester, Manchester, UK; 3Intensive Care Department, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium; 4Haut Leveque University Hospital of Bordeaux, University of Bordeaux 2, Pessac, France; 5Intensive Care Department, East Limburg Hospital, Genk, Belgium Abstract: Acid–base disorders are common in the critically ill. Most of these disorders do not cause harm and are self-limiting after appropriate resuscitation and management. Unfortunately, clinicians tend to think about an acid–base disturbance as a “disease” and spend long hours effectively treating numbers rather than the patient. Moreover, a sizable number of intensive-care physicians experience difficulties in interpreting the significance of or understanding the etiology of certain forms of acid–base disequilibria. Traditional tools for interpreting acid–base disorders may not be adequate for analyzing the complex nature of these metabolic abnormalities. Inappropriate interpretation may also lead to wrong clinical conclusions and incorrectly influence clinical management (eg, bicarbonate therapy for metabolic acidosis in different clinical situations). The Stewart approach, based on physicochemical principles, is a robust physiological concept that can facilitate the interpretation and analysis of simple, mixed, and complex acid–base disorders, thereby allowing better diagnosis of the cause of the disturbance and more timely treatment. However, as the concept does not attach importance to plasma bicarbonate, clinicians may find it complicated to use in their daily clinical practice. This article reviews various approaches to interpreting acid–base disorders and suggests the integration of base-excess and Stewart approach for a better interpretation of these metabolic disorders. Keywords: hemofiltration, strong ion difference, strong ion gap, dialysis, CRRT, sepsis, bedside acid–base approach, Stewart acid base approach

S Lochy,1 R Jacobs,1 PM Honoré,1 E De Waele,1 O Joannes-Boyau,2 J De Regt,1 V Van Gorp,1 HD Spapen1 1Intensive Care Dept, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium; 2Haut Leveque University Hospital of Bordeaux, University of Bordeaux 2, Pessac, France Abstract: Acute phosphate nephropathy or nephrocalcinosis is a tubulointerstitial nephropathy characterized by tubular calcium phosphate deposition – crystal nephropathy – and slowly progressive renal insufficiency during or following treatment with preparations containing sodium phosphate. We report a patient who developed nephrocalcinosis (crystal induced acute kidney injury) following the administration of a combination of oral and rectal sodium phosphate for treatment of postoperative constipation. A timely renal replacement therapy procedure may reverse the process of crystallization and the irreversible slope towards chronic dialysis. Keywords: hemofiltration, acute phosphate nephropathy, hyperphosphatemie, crystal induced nephropathy, CRRT, worse prognosis, dialysis

Patrick M Honore,1 Rita Jacobs,1 Inne Hendrickx,1 Elisabeth De Waele,1 Viola Van Gorp,1 Olivier Joannes-Boyau,2 Jouke De Regt,1 Willem Boer,3 Herbert D Spapen1 1Intensive Care Unit, Universitair Ziekenhuis Brussel, VUB University, Brussels, Belgium; 2Intensive Care Unit, Hopital Haut Leveque, University of Bordeaux 2, Bordeaux, France; 3Intensive Care Unit, Ziekenhuis Oost-Limburg, Genk, Belgium Abstract: Biomarkers have emerged as exemplary key players in translational medicine. Many have been assessed for timely recognition, early treatment, and adequate follow-up for a variety of pathologies. Biomarker sensitivity has improved considerably over the last years but specificity remains poor, in particular when two “marker-sensitive” conditions overlap in one patient. Biomarker research holds an enormous potential for diagnostic and prognostic purposes in postoperative and critically ill patients who present varying degrees of inflammation, infection, and concomitant (sub)acute organ dysfunction or failure. Despite a remarkable progress in development and testing, biomarkers are not yet ready for routine use at the bedside. Keywords: biomarkers, acute kidney injury, sepsis, ARDS

Patrick M Honore,1 Rita Jacobs,1 Elisabeth De Waele,1 Viola Van Gorp,1 Jouke De Regt,1 Olivier Joannes-Boyau,2 Willem Boer,3 Herbert D Spapen1 1Intensive Care Department, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium; 2Intensive Care Unit, Haut Leveque University Hospital of Bordeaux, University of Bordeaux 2, Pessac, France; 3Intensive Care Department, Ziekenhuis Oost Limburg, Genk, Belgium Abstract: Recent case reports of acute esophageal necrosis in patients with chronic kidney disease (CKD) undergoing hemodialysis encouraged us to look beyond hypoperfusion/ischemia as a sole explanation for this dramatic complication. At least three intriguing pathways, ie, accumulation of protein-bound toxins, endotoxin translocation, and altered mucosal defense mechanisms, have been proposed to explain the inherent susceptibility of CKD patients to developing ischemia-related and cardiovascular events. Interestingly, all the proposed pathways can be potentially antagonized or attenuated. At present, however, it is not known whether one pathway predominates or if any interaction exists between these pathways. More solid experimental and clinical data are warranted to acquire a better insight into the complex pathogenesis of CKD-associated ischemia. Keywords: chronic kidney disease, ischemia, pathophysiology, cardiovascular events

Patrick M Honore,1 Rita Jacobs,1 Stijn Lochy,1 Elisabeth De Waele,1 Viola Van Gorp,1 Jouke De Regt,1 Geert Martens,1 Olivier Joannes-Boyau,2 Willem Boer,3 Herbert D Spapen1 1Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium; 2Haut Leveque University Hospital of Bordeaux, University of Bordeaux 2, Pessac, France; 3Ziekenhuis Oost-Limburg, Genk, Belgium Abstract: We describe a patient with severe New Delhi metallo-β-lactamase-1 Escherichia coli infection who developed convulsions rapidly followed by acute respiratory muscle weakness and apnea while receiving intravenous colistin. Toxic levels of colistin were rapidly removed by hemofiltration and, more specifically, by hemoadsorption. Keywords: colistin, neurotoxicity, convulsions, neuromuscular blockade, apnea, hemofiltration, hemoadsorption, CVVH, CRRT

Background: Rezafungin is an echinocandin approved in the US and EU to treat candidaemia and/or invasive candidiasis. This post-hoc, pooled analysis of the Phase 2 STRIVE and Phase 3 ReSTORE trials assessed rezafungin versus caspofungin in patients with candidaemia and/or invasive candidiasis (IC) in the intensive care unit (ICU) at randomisation., Methods: STRIVE and ReSTORE were randomised double-blind trials in adults with systemic signs and mycological confirmation of candidaemia and/or IC in blood or a normally sterile site ≤ 96 h before randomisation. Data were pooled for patients in the ICU at randomisation who received intravenous rezafungin (400 mg loading dose then 200 mg once weekly) or caspofungin (70 mg loading dose then 50 mg once daily) for ≤ 4 weeks. Outcomes were Day 30 all-cause mortality (primary outcome), Day 5 and 14 mycological eradication, time to negative blood culture, mortality attributable to candidaemia/invasive candidiasis, safety, and pharmacokinetics., Results: Of 294 patients in STRIVE/ReSTORE, 113 were in the ICU at randomisation (rezafungin n = 46; caspofungin n = 67). At baseline, ~ 30% of patients in each group had impaired renal function and/or an Acute Physiologic Assessment and Chronic Health Evaluation II score ≥ 20. One patient (in the caspofungin group) was neutropenic at baseline. Day 30 all-cause mortality was 34.8% for rezafungin versus 25.4% for caspofungin. Day 5 and 14 mycological eradication was 78.3% and 71.7% for rezafungin versus 59.7% and 65.7% for caspofungin, respectively. Median time to negative blood culture was 18 (interquartile range, 12.6-43.0) versus 38 (interquartile range, 15.9-211.3) h for rezafungin versus caspofungin (stratified log-rank P = 0.001; nominal, not adjusted for multiplicity). Candidaemia/IC-attributable deaths occurred in two rezafungin patients versus one caspofungin patient. Safety profiles were similar between groups. Overall, 17.4% (rezafungin) versus 29.9% (caspofungin) of patients discontinued due to treatment-emergent adverse events. Rezafungin exposure following the initial 400-mg dose was comparable between patients in the ICU at randomisation (n = 50) and non-ICU patients (n = 117)., Conclusions: Rezafungin was well tolerated and efficacious in critically ill, mainly non-neutropenic patients with candidaemia and/or IC. This analysis provides additional insights into the efficacy and safety of rezafungin in the ICU population., (© 2024. The Author(s).)

Background: Invasive aspergillosis (IA) is a significant cause of morbidity and mortality in patients with haematological malignancies. Accurate diagnosis of IA is challenging due to non-specific symptoms and the impact of antifungal prophylaxis on biomarker sensitivity., Methods: This retrospective study evaluated the diagnostic performance of three serum biomarkers: Aspergillus Galactomannan Ag VirClia Monotest ® (VirClia), Wako β-D-Glucan Test ® (Wako BDG), and MycoGENIE Real-Time PCR ® (MycoGENIE PCR). True positives were defined as patients with proven or probable IA ( n = 14), with a positive Platelia Aspergillus Antigen ® (Platelia) serving as a mycological criterion. True negatives were identified as patients with a positive Platelia assay but classified as non-probable IA ( n = 10) and outpatients who consistently tested negative with the Platelia test throughout the study period ( n = 20)., Results: Most patients diagnosed with proven or probable IA were acute myeloid leukaemia or myelodysplastic syndrome patients receiving mould-active antifungal prophylaxis or treatment (71%). VirClia demonstrated high sensitivity (100%) for detecting IA, with a specificity of 83%. Wako BDG and MycoGENIE PCR showed lower sensitivities for IA (57% and 64%, respectively). MycoGENIE PCR detected Aspergillus spp. and Mucorales in two patients., Conclusions: Accurate diagnosis of IA remains challenging, especially in patients who have received mould-active antifungal treatment. VirClia showed comparable performance to Platelia, suggesting its potential for routine use. However, Wako BDG and MycoGENIE PCR results were less favourable in our study cohort. Nevertheless, MycoGENIE PCR detected two probable co-infections with Aspergillus spp. and Mucorales .

BACKGROUND CRS (cytokine release syndrome) is a massive activation of the inflammatory system characterized by a supra-physiological rate of inflammatory cytokines. The interleukin 6 cytokine plays a central role in CRS. The main clinical sign of CRS is fever, but CRS can lead to multiple organ failure in severe cases. CRS is usually described in sepsis, more recently in SARS COV-2 infection, and in chimeric antigen receptor T-cell therapy. However, it can also be associated with immune checkpoint inhibitors (ICIs), which is infrequently described. ICI have growing indications and can lead to CRS by causing an uncontrolled activation of the immune system. There are currently no treatment guidelines for ICI-induced CRS. CASE REPORT We report a rare case of grade 3 CRS induced by nivolumab associated with 5-fluorouracil and oxaliplatin for gastric cancer. The patient was 65-year-old man with an adenocarcinoma of the cardia. CRS developed during the tenth course of treatment and was characterized by fever, hypotension requiring vasopressors, hypoxemia, acute kidney injury, and thrombopenia. The patient was transferred quickly to the Intensive Care Unit. He was treated for suspected sepsis, but it was ruled out after multiple laboratory examinations. There was rapid resolution after infusion of hydrocortisone. CONCLUSIONS The use of ICIs is expanding. Nivolumab-induced CRS is rarely described but can be severe and lead to multiple organ dysfunction; therefore, intensive care practitioners should be informed about this adverse effect. More studies are needed to better understand this condition and establish treatment guidelines.

The optimization of patients' treatment in the intensive care unit (ICU) needs a lot of information and literature analysis. Many changes have been made in the last years to help evaluate sedated patients by scores to help take care of them. Patients were completely sedated and had continuous intravenous analgesia and neuromuscular blockades. These three drug classes were the main drugs used for intubated patients in the ICU. During these last 20 years, ICU management went from fully sedated to awake, calm, and nonagitated patients, using less sedatives and choosing other drugs to decrease the risks of delirium during or after the ICU stay. Thus, the usefulness of these three drug classes has been challenged. The analgesic drugs used were primarily opioids but the use of other drugs instead is increasing to lessen or wean the use of opioids. In severe acute respiratory distress syndrome patients, neuromuscular blocking agents have been used frequently to block spontaneous respiration for 48 hours or more; however, this has recently been abolished. Optimizing a patient's comfort during hemodynamic or respiratory extracorporeal support is essential to reduce toxicity and secondary complications., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Saudi Journal of Anesthesia.)

Purpose of Review: Hyperammonaemia is almost always develops in patients with severe liver failure and this remains the commonest cause of elevated ammonia concentrations in the ICU. Nonhepatic hyperammonaemia in ICU presents diagnostic and management challenges for treating clinicians. Nutritional and metabolic factors play an important role in the cause and management of these complex disorders., Recent Findings: Nonhepatic hyperammonaemia causes such as drugs, infection and inborn errors of metabolism may be unfamiliar to clinicians and risk being overlooked. Although cirrhotic patients may tolerate marked elevations in ammonia, other causes of acute severe hyperammonaemia may result in fatal cerebral oedema. Any coma of unclear cause should prompt urgent measurement of ammonia and severe elevations warrant immediate protective measures as well as treatments such as renal replacement therapy to avoid life-threatening neurological injury., Summary: The current review explores important clinical considerations, the approach to testing and key treatment principles that may prevent progressive neurological damage and improve outcomes for patients with hyperammonaemia, especially from nonhepatic causes., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Invasive candidiasis or candidemia is a severe infection affecting more than 250,000 people worldwide every year. It is present in up to 16% of ICU patients. The prognosis of these infections is unfavorable, with global death estimated around 50,000 per year, which corresponds to up to 40% depending on patient severity and comorbidities. Therapeutic failure is not rare due to the emergence of multiresistant strains and of new species poorly responsive to current therapies like Candida auris., Areas Covered: We first review the positioning of antifungal drugs used to treat candidiasis, namely polyenes, azoles, echinocandins and pyrimidine analogues. We then discuss the progresses brought by new formulations, new derivatives within these classes, compounds acting on new targets or repurposed drugs in terms of pharmacokinetic profile, spectrum of activity, potency, safety or risk of drug-drug interactions., Expert Opinion: While new formulations (amphotericin B cochleate) improve oral bioavailability of the corresponding drugs, new azoles or echinocandins offer higher potency including against strains resistant to former generations of drugs. Repurposed drugs show synergism with current therapies in vitro. Results from ongoing and future clinical trials will be decisive to establish the interest for these drugs in our arsenal.

Background: This study aimed to observe the effects of a fast acute ascent to simulated high altitudes on cardiovascular function both in the main arteries and in peripheral circulation. Methods: We examined 17 healthy volunteers, between 18 and 50 years old, at sea level, at 3842 m of hypobaric hypoxia and after return to sea level. Cardiac output (CO) was measured with Doppler transthoracic echocardiography. Oxygen delivery was estimated as the product of CO and peripheral oxygen saturation (SpO2). The brachial artery’s flow-mediated dilation (FMD) was measured with the ultrasound method. Post-occlusion reactive hyperemia (PORH) was assessed by digital plethysmography. Results: During altitude stay, peripheral oxygen saturation decreased (84.9 ± 4.2% of pre-ascent values; p < 0.001). None of the volunteers presented any hypoxia-related symptoms. Nevertheless, an increase in cardiac output (143.2 ± 36.2% of pre-ascent values, p < 0.001) and oxygen delivery index (120.6 ± 28.4% of pre-ascent values; p > 0.05) was observed. FMD decreased (97.3 ± 4.5% of pre-ascent values; p < 0.05) and PORH did not change throughout the whole experiment. Τhe observed changes disappeared after return to sea level, and normoxia re-ensued. Conclusions: Acute exposure to hypobaric hypoxia resulted in decreased oxygen saturation and increased compensatory heart rate, cardiac output and oxygen delivery. Pre-occlusion vascular diameters increase probably due to the reduction in systemic vascular resistance preventing flow-mediated dilation from increasing. Mean Arterial Pressure possibly decrease for the same reason without altering post-occlusive reactive hyperemia throughout the whole experiment, which shows that compensation mechanisms that increase oxygen delivery are effective.

Competing Interests: Conflict of Interest Patrick M. Honoré is the Editor-in-Chief of the journal. The article was subject to the journal's standard procedures, with peer review handled independently of this editor and his research group.

Background: Creatinine is distributed between the intracellular and extracellular compartments, and as a result, the measurement of its concentration is strongly related to the fluid status of the patient. An interest has been shown in correcting measured serum creatinine levels according to the fluid balance in order to better specify the degree of acute kidney injury (AKI)., Methods: We conducted a retrospective observational study of 33 children, aged 0 to 5 years, admitted to the pediatric intensive care unit for acute respiratory distress syndrome treated by extracorporeal membrane oxygenation. We compared measured and corrected creatinine and assessed the degree of agreement between these values using both Cohen's kappa and Krippendorff's alpha coefficient., Results: In our cohort, 37% of the classifications made according to measured creatinine levels were erroneous and, in the majority of cases, the degree of AKI was underestimated., Conclusion: Correction of the measured creatinine value according to the degree of fluid overload may result in more accurate diagnosis of AKI. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2021. IPNA.)

Background: Acute bronchiolitis is the most frequent cause of respiratory distress in pediatric emergency medicine. The risk of respiratory failure is frequently over evaluated, and results in systematic vascular access., Methods: We conducted a prospective observational study in children under 18 months of age hospitalized for bronchiolitis. The aim of the study was to evaluate whether catheter insertion was useful for management. We monitored the number of catheters inserted in the emergency department and their subsequent use for rapid sequence intubation, adrenaline administration, or antimicrobial therapy. We recorded the number of secondary pediatric intensive care unit (ICU) admissions., Results: We followed 162 patients and compared two populations, children with (population A, n = 35) and without (population B, n = 127) catheter insertion. There were no significant differences in age, oxygen saturation, heart rate, c-reactive protein, neutrophil count and the number of times nebulization was conducted at admission. Population A compared to B had a significantly higher temperature (38.1 ± 0.9 vs . 37.6 ± 0.7°C, P = 0.004) and respiratory rate (64 ±13 vs . 59 ±17, P = 0.033). Twelve patients were secondarily transferred to pediatric ICU, 3 from population A and 9 from B (NS). In a multivariate analysis, no significant relationship was found between ICU admission, venous access placement and potential confounding factors (pneumonia, age < 6 months, age < 3 months, food intake < 60%, temperature > 38° C, heart rate > 180 bpm, respiratory rate > 60/min, SpO 2 < 95%, Spo 2 < 90%, oxygen therapy, positive respiratory syncytial virus [RSV] sampling). Except for antimicrobial therapy ( n = 32), catheters inserted in the emergency department were used in 5 patients for intravenous rehydration and in one patient in pediatric ICU for rapid sequence intubation., Conclusions: There were no life-threatening events that required immediate venous access for cardiopulmonary resuscitation. Medical treatment could be administered orally or via nasogastric tube in most cases. Peripheral catheterization was useless in immediate emergency management and only one child required a differed rapid sequence intubation., Competing Interests: Conflict of interest Patrick M. Honore is the Co-Eidtor-in-Chief of the journal. This article was subject to the journal's standard procedures, with peer review handled independently of this editor and his research groups., (© 2021 Sébastien Redant,Nora Nehar-Stern, Patrick M. Honoré, Rachid Attou, Caroline Haggenmacher, Ashita Tolwani, David De Bels, Dominique Biarent, published by Sciendo.)

Objective: Severe acute respiratory syndrome coronavirus-2 acute kidney injury is a condition that in many ways resembles classical acute kidney injury. The pathophysiology appears to be multifactorial, and accordingly, our main objective was to review possible components of this form of acute kidney injury., Data Sources: Literature review., Data Synthesis: Our principal observation was that the various components of severe acute respiratory syndrome coronavirus-2 acute kidney injury appear to be relatively similar to the classical forms. Temporality of injury is an important factor but is not specific to severe acute respiratory syndrome coronavirus-2 acute kidney injury. Several insults hit the kidney at different moments in the course of disease, some occurring prior to hospital admission, whereas others take place at various stages during hospitalization., Conclusions and Relevance: Treatment of severe acute respiratory syndrome coronavirus-2 acute kidney injury cannot be approached in a "one-size-fits-all" manner. The numerous mechanisms involved do not occur simultaneously, leading to a multiple hit model that may contribute to the prevalence and severity of acute kidney injury. A personalized approach to each patient with acute kidney injury based on the timing and severity of disease is necessary in order to provide appropriate treatment. Although data from the literature regarding the previous coronavirus infections can give some insights, more studies are needed to explore the different mechanisms of acute kidney injury occurring as a result of severe acute respiratory syndrome coronavirus-2., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Continuous renal replacement therapy (CRRT) is associated with micronutrients loss. Current recommendations are to administer 1-1.5g/kg/day of proteins during CRRT. We aim to evaluate the net effect of CRRT on amino acids (AA), vitamins A and C (Vit A, Vit C) levels., Methods: This is a prospective observational study embedded within a randomised controlled trial comparing two CRRT doses in patients with septic shock. CRRT was provided in continuous veno-venous haemofiltration mode at a dose of either 35ml/kg/h or 70ml/kg/h. All patients received parenteral nutrition with standard trace elements and vitamins (protein intake 1g/kg/d). We measured serum levels of glutamine, valine and alanine as well as Vit A and Vit C upon randomisation, study day four and eight. In addition, we measured a larger panel of AA in a subset of 11 patients., Results: We included 30 patients (17 allocated to 70ml/kg/h and 13 to 35ml/kg/h CRRT). Before CRRT initiation, mean plasma levels of glutamine and valine, Vit A and Vit C were low. CRRT was not associated with any significant change in AA levels except for a decrease in cystein. It was associated with an increase in Vit A and a decrease in Vit C levels. CRRT dose had no impact on those nutrients blood levels., Conclusions: Irrespective of dose, CRRT was associated with a decrease in cysteine and Vit C and an increase in Vit A with no significant change in other AA. Further studies should focus on lean mass wasting during CRRT., (Copyright © 2021 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

The high mortality of pediatric acute respiratory distress syndrome (PARDS) is partly related to fluid overload. Extracorporeal membrane oxygenation (ECMO) is used to treat pediatric patients with severe PARDS, but can result in acute kidney injury (AKI) and worsening fluid overload. The objective of this study was to determine whether the addition of CRRT to ECMO in patients with PARDS is associated with increased mortality., Methods: We conducted a retrospective 7-year study of patients with PARDS requiring ECMO and divided them into those requiring CRRT and those not requiring CRRT. We calculated severity of illness scores, the amount of blood products administered to both groups, and determined the impact of CRRT on mortality and morbidity., Results: We found no significant difference in severity of illness scores except the vasoactive inotropic score (VIS, 45 ± 71 vs. 139 ± 251, p = 0.042), which was significantly elevated during the initiation and the first three days of ECMO. CRRT was associated with an increase in the use of blood products and noradrenaline ( p < 0.01) without changing ECMO duration, length of PICU stay or mortality., Conclusion: The addition of CRRT to ECMO is associated with a greater consumption of blood products but no increase in mortality.

Background: Hyperammonemia caused by a disorder of the urea cycle is a rare cause of metabolic encephalopathy that may be underdiagnosed by the adult intensivists because of its rarity. Urea cycle disorders are autosomal recessive diseases except for ornithine transcarbamylase deficiency (OTCD) that is X-linked. Optimal treatment is crucial to improve prognosis. Main body We systematically reviewed cases reported in the literature on hyperammonemia in adulthood. We used the US National Library of Medicine Pubmed search engine since 2009. The two main causes are ornithine transcarbamylase deficiency followed by type II citrullinemia. Diagnosis by the intensivist remains very challenging therefore delaying treatment and putting patients at risk of fatal cerebral edema. Treatment consists in adapted nutrition, scavenging agents and dialysis. As adults are more susceptible to hyperammonemia, emergent hemodialysis is mandatory before referral to a reference center if ammonia levels are above 200 µmol/l as the risk of cerebral edema is then above 55%. Definitive therapy in urea cycle abnormalities is liver transplantation., Conclusion: Awareness of urea cycle disorders in adults intensive care units can optimize early management and accordingly dramatically improve prognosis. By preventing hyperammonemia to induce brain edema and herniation leading to death.

Even today, little is known about the pathophysiology of the post-resuscitation syndrome. Our narrative review is one of the first summarizing all the knowledge about this phenomenon. We have focused our review upon the potential role of blood purification in attenuating the consequences of the post-resuscitation syndrome. Blood purification can decrease the cytokine storm particularly when using a CytoSorb absorber. Acrylonitrile 69-based oXiris membranes can remove endotoxin and high-mobility group box 1 protein. Blood purification techniques can quickly induce hypothermia. Blood purification can be used with veno-arterial extracorporeal membrane oxygenation to remove excess water. Further trials are needed to provide more concrete data about the use of blood purification in the post-resuscitation syndrome., (© 2021 S. Karger AG, Basel.)

The principles and use of plasmapheresis are often little understood by intensivists. We propose to review the principles, the main indications, and the methods of using this technique., (© 2020 S. Karger AG, Basel.)

Extracorporeal CO2 removal within a continuous renal replacement therapy circuit offers multiple advantages for the regulation of the CO2 extraction. The authors review the impact of the dialysate solution, the buffer, and the anticoagulation on CO2 removal. They propose a theoretical model of the ideal circuit for the optimization of CO2 extraction., (© 2020 S. Karger AG, Basel.)

Background: Correcting hyponatremia too quickly can lead to osmotic demyelination syndrome. During citrate dialysis, a significant sodium load is brought to the prefilter. We reviewed the impact of this sodium load on the evolution of sodium levels in patients undergoing continuous renal replacement therapy with citrate anticoagulation., Materials and Methods: The medical records of 5 patients with hyponatremia who received dialysis with citrate anticoagulation, over a 10-year period, were reviewed. The sodium of the dialysate and of the reinjection fluid was adapted according to the serum sodium level recommended by the guidelines of the time. Data from the first 24 h after initiation of dialysis was evaluated., Results: The difference in serum sodium levels between day 1 and day 2 was statistically significant, with a rise of 7.8 ± 3.7 mmol/L., Discussion: The mean serum sodium increase in our series of patients did not exceed the increase of 10-12 mEq/L/day permitted by the guidelines. The excess sodium was absorbed by the filter., Conclusion: In this small series of patients, with adjustment of the sodium concentration of dialysate and reinjection fluid, the use of citrate was found to be safe., (© 2020 S. Karger AG, Basel.)

Background and Objectives: SARS-CoV-2-induced ARDS is a new entity that should be characterized as it appears to be different from standard ARDS. Hypernatremia is a biological alteration that seems to occur very often in this population without any clear cause. The present study aims to clarify the possible causes of hypernatremia and evaluate its impact on patient outcome., Patients and Methods: We conducted a retrospective one-day prevalence study in 2 intensive care units, which only treated COVID-19 patients with moderate to severe ARDS. We measured blood and urine electrolytes in all the patients. Patients with chronic renal failure or renal replacement therapy were excluded from the study. Hypernatremia was defined as plasma sodium levels above 145 mmol/L., Results: Inclusion criteria were met in 17 out of 24 patients. Hypernatremia was present in 52% patients. All had a natriuresis higher than 20 mmol/L and a urine osmolality above 600 mOsm/L. Hypernatremia was acquired in ICU as all the patients had a normal serum sodium level at admission., Conclusion: The incidence of hypernatremia was elevated and appears to be linked to significant insensible water losses. This should trigger us to optimize the maintenance fluid therapy in critically ill patients with SARS-CoV-2-induced ARDS., Competing Interests: Conflict of Interest Conflict of interests: The authors have no conflicts of interest to declare., (© 2020 Sébastien Redant, Julien Vanderhulst, Evelyne Maillart, Rachid Attou, Andrea Gallerani, Patrick M. Honoré, David De Bels, published by Sciendo.)

Competing Interests: Conflict of Interest Conflict of Interests: The authors declare to have no competing interests.

Gas gangrene (GG) remains a life-threatening and deadly disease. Early recognition together with daily surgical debridement remains the mainstay of therapy. We sought to describe a fatal case of necrotizing soft tissue infection, which was a gas gagrene in this case. This case was remarkable as two main sites were infected simultaneously in geographical zones very far from each other making dissemination between both sites almost impossible. The other particularity was the fact that the infection was caused at the same time by four different bacteria that is atypical in GG similar to that in streptoccocal necrotizing fasciitis where one bacteria is the causative agent ( Clostridium perfringens for GG and group A streptococcus for necrotizing fasciitis)., Competing Interests: Conflict of Interest Conflict of Interests: The authors declare to have no competing interests., (© 2020 Thierry Preseau, Jacques Deviendt, Ruth Duttman, Rachid Attou, Diane Franck, Ruben Claeys, Patrick M. Honoré, David De Bels, published by Sciendo.)

Introduction: Potassium abnormalities are frequent in intensive care but their incidence in the emergency department is unknown., Aim: We describe the spectrum of potassium abnormalities in our tertiary-level pediatric emergency department., Methods: Retrospective case-control study of all the patients admitted to a single-center tertiary emergency department over a 2.5-year period. We compared patients with hypokalemia (<3.0mEq/L) and patients with hyperkalemia (>6.0mEq/L) against a normal randomized population recruited on a 3:1 ratio with potassium levels between 3.5 and 5mEq/L., Results: Between January 1, 2013 and August 31, 2016 we admitted 108,209 patients to our emergency department. A total of 9342 blood samples were tested and the following potassium measurements were found: 60 cases of hypokalemia (2.8±0.2mEq/L) and 55 cases of hyperkalemia (6.4±0.6mEq/L). In total, 200 patients with normokalemia were recruited (4.1±0.3mEq/L). The main causes of the disorders were non-specific: lower respiratory tract infection (23%) and fracture (15%) for hypokalemia, lower respiratory tract (21.8%) and ear-nose-throat infections (20.0%) for hyperkalemia. Patients with hyperkalemia had an elevated creatinine level (0.72±1.6 vs. 0.40±0.16mg/dL, P<0.0001) with lower bicarbonate (19.4±3.8 vs. 21.8±2.8mmol/L, P=0.0001) and higher phosphorus levels (1.95±0.6 vs. 1.42±0.27mg/dL, P=0.0001). Patients with hypokalemia had an elevated creatinine level (0.66±0.71 vs. 0.40±0.16mg/dL, P<0.0001) and a lower phosphorus level (1.12±0.31 vs. 1.42±0.27mg/dL, P=0.0001). We did not observe significant differences in pH, PCO 2 , base excess and lactate, or in the mean duration of hospitalization in general wards and pediatric intensive care units according to the PIM and PRISM scores., Discussion: Dyskalemia is rare in emergency department patients: 0.64% for hypokalemia and 0.58% for hyperkalemia. This condition could be explained by a degree of renal failure due to transient volume disturbance. The main mechanism is dehydration due to digestive losses, polypnea in young patients, and poor intake. In the case of hypokalemia, poor intake and digestive losses could be the main explanation. These disorders resolve easily with feeding or perfusion and do not impair development., Conclusion: Dyskalemia is rare in emergency department patients and is easily resolved with feeding or perfusion. A plausible etiological mechanism is a transient volume disturbance. Dyskalemia is not predictive of poor development in the emergency pediatric population., (Copyright © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Background and Objectives: High-dose colistin (COL) ensures adequate treatment of pneumonia caused by multidrug resistant gram-negative bacteria (MDR-GNB) but must be weighed against a higher risk of nephrotoxicity. Continuous veno-venous hemofiltration (CVVH) clears COL by filtering and membrane adsorption that permits to avoid dose accumulation and excessively high peak concentrations. We evaluated clinical/microbiological efficacy of the high-dose COL treatment under CVVH in patients with newly diagnosed MDR-GNB ventilator-associated pneumonia (VAP)., Methods: Observational cohort study in critically ill adult patients with MDR-GNB VAP. Colistimethate sodium (CMS) was administered as a 9 million international units (MIU) of loading dose followed by 3 × 4.5 MIU daily. CVVH was performed over a highly adsorptive membrane. Clinical and microbiological efficacies were assessed at the end of therapy. In survivors, serum creatinine level was evaluated before and at the end of therapy., Results: Fourteen patients (8 male patients, aged 57 ± 14 years) were consecutively included. Isolated pathogens were Pseudomonas aeruginosa in 7, Klebsiella pneumoniae in 5, and other Enterobacteriaceae in 2 patients. A favorable clinical response was observed in 9 patients (64%). Full and presumed microbiological eradication was observed in 12 patients (86%). Two patients were diagnosed with Stage 1 acute kidney injury., Conclusions: In patients with MDR-GNB VAP, CVVH may represent an interesting option to enable effective high-dose COL treatment., Competing Interests: Conflict of Interest There is no competing interest related to the article., (© 2019 Herbert Spapen, Johan van Laethem, Maya Hites, An Verdoodt, Marc Diltoer, Patrick M. Honoré, published by Sciendo.)

Objective: To observe the effects of a fast-acute ascent to high altitude on brain cognitive function and transcranial doppler parameters in order to understand the physiological countermeasures of hypoxia., Methods: 17 high-altitude-naïve male subjects (mean age was 26.3 ± 8.1 years) participated in the study. We measured Critical Flicker Fusion Frequency (CFFF), blood oxygen saturation, Psychology Experiment Building (PEBL) including three tests (Modified Math Processing Task, Perceptual Vigilance Task, and Time Estimation Task), as well as Cerebral Blood Flow index (CBFi), mean cerebral artery Systolic and diastolic velocities, Cerebral Pulsatility index (CPi), and heart Rate. All were measured at sea level, at least 1 h after arrival at the hypobaric hypoxia equivalent of 3842 m and 1 h after return to sea level., Results: Under acute exposure to hypobaric hypoxic conditions, significant decrease in CFFF [42.1 ± 1 vs. 43.5 ± 1.7 Hz at sea level (asl), p < 0.01], CBFi (611 ± 51 vs. 665 ± 71 asl, p < 0.01) and blood oxygen saturation (83 ± 4% vs. 98 ± 1% asl, p < 0.001) as compared to pre-ascent values were observed. Physiological countermeasures to hypoxia could be involved as there was no significant change in neuropsychometric tests, Systolic and Diastolic velocities and CPi. A significant increase in Heart Rate (81 ± 15 bpm vs. 66 ± 15 bpm asl, p < 0.001) was observed. All parameters returned to their basal values 1 h after regaining sea level., Conclusion: Hypoxia results in a decrease in CFFF, CBFi and oxygen saturation and in an increase in heart rate. As it decreased, Cerebral Blood Flow index does not seem to be the physiological measurement of choice to hypoxia explaining the maintenance of cognitive performance after acute exposure to hypobaric hypoxia and requires further investigation. Cerebral oxygen delivery and extraction could be one of the underlying mechanisms.