Importance:The effect of sodium bicarbonate infusion on outcome in patients with severe metabolic acidemia and moderate to severe acute kidney injury is unknown. Objective:To determine whether sodium bicarbonate infusion is associated with day 90 all-cause mortality in patients with severe metabolic acidemia and moderate to severe acute kidney injury. Design, Setting, and Participants:Randomized, open-label, clinical trial conducted with 640 patients in 43 French intensive care units from October 6, 2019, to December 19, 2023, with 90-day follow-up. The last date of follow-up was June 17, 2024. Adults with severe metabolic acidemia (defined as pH ≤7.20) and moderate to severe acute kidney injury were enrolled. Intervention:Patients were randomized 1:1 to receive either intravenous sodium bicarbonate infusion or no sodium bicarbonate to target an arterial pH of 7.30 or higher. Main Outcomes and Measures:The primary outcome was day 90 all-cause mortality. Secondary outcomes included day 28 and day 180 all-cause mortality; use of organ support therapy, vasopressors, or invasive mechanical ventilation; intensive care unit and hospital length of stay; intensive care unit-acquired infections; fluid balance; day-7 Sequential [Sepsis-related] Organ Failure Assessment score (6 organ systems' function is evaluated and scored from 0 [no dysfunction] to 4 [failure]; total score ranges from 0 [normal] to 24 [maximum failure]); and major adverse kidney events on day 90. Results:Among 640 randomly assigned patients, 627 were analyzed (313 in the control group and 314 in the bicarbonate group). The median age was 67 years (IQR, 59-74 years); 194 of 314 patients (62%) in the bicarbonate group and 185 of 313 controls (59%) were male. In the primary analysis, day 90 all-cause mortality was 195 of 314 patients (62.1%) in the bicarbonate group and 193 of 313 (61.7%) in the control group (absolute difference, 0.4; 95% CI, -7.2 to 8.0; P = .91). There was no evidence of a group effect on day 28 or day 180 all-cause mortality. Among 18 secondary outcomes, kidney replacement therapy was used in 109 of 314 (35%) bicarbonate group patients and 157 of 313 (50%) controls (absolute difference, -15.5; 95% CI, -23.1 to -7.8). No evidence of a group effect was found on other secondary outcomes, including adverse events. Conclusions and Relevance:For patients with severe metabolic acidemia and moderate to severe acute kidney injury, intravenous sodium bicarbonate did not affect mortality. Trial Registration:ClinicalTrials.gov Identifier: NCT04010630.

The effect of sodium bicarbonate infusion on outcome in patients with severe metabolic acidemia and moderate to severe acute kidney injury is unknown. To determine whether sodium bicarbonate infusion is associated with day 90 all-cause mortality in patients with severe metabolic acidemia and moderate to severe acute kidney injury. Randomized, open-label, clinical trial conducted with 640 patients in 43 French intensive care units from October 6, 2019, to December 19, 2023, with 90-day follow-up. The last date of follow-up was June 17, 2024. Adults with severe metabolic acidemia (defined as pH ≤7.20) and moderate to severe acute kidney injury were enrolled. Patients were randomized 1:1 to receive either intravenous sodium bicarbonate infusion or no sodium bicarbonate to target an arterial pH of 7.30 or higher. The primary outcome was day 90 all-cause mortality. Secondary outcomes included day 28 and day 180 all-cause mortality; use of organ support therapy, vasopressors, or invasive mechanical ventilation; intensive care unit and hospital length of stay; intensive care unit–acquired infections; fluid balance; day-7 Sequential [Sepsis-related] Organ Failure Assessment score (6 organ systems’ function is evaluated and scored from 0 [no dysfunction] to 4 [failure]; total score ranges from 0 [normal] to 24 [maximum failure]); and major adverse kidney events on day 90. Among 640 randomly assigned patients, 627 were analyzed (313 in the control group and 314 in the bicarbonate group). The median age was 67 years (IQR, 59-74 years); 194 of 314 patients (62%) in the bicarbonate group and 185 of 313 controls (59%) were male. In the primary analysis, day 90 all-cause mortality was 195 of 314 patients (62.1%) in the bicarbonate group and 193 of 313 (61.7%) in the control group (absolute difference, 0.4; 95% CI, −7.2 to 8.0; P = .91). There was no evidence of a group effect on day 28 or day 180 all-cause mortality. Among 18 secondary outcomes, kidney replacement therapy was used in 109 of 314 (35%) bicarbonate group patients and 157 of 313 (50%) controls (absolute difference, −15.5; 95% CI, −23.1 to −7.8). No evidence of a group effect was found on other secondary outcomes, including adverse events. For patients with severe metabolic acidemia and moderate to severe acute kidney injury, intravenous sodium bicarbonate did not affect mortality. ClinicalTrials.gov Identifier: NCT04010630

Les infections urinaires en Réanimation regroupent plusieurs situations cliniques allant des bactériuries asymptomatiques ou peu symptomatiques aux infections urinaires sévères avec atteinte systémique ou urosepsis. Un urosepsis est en cause dans environ 10% des admissions pour choc septique en secteurs de soins critiques. Il est d’origine communautaire ou associé aux soins et s’accompagne dans un grand nombre de cas d’une uropathie sous-jacente ou d’une obstruction des voies urinaires. Dans cette revue, le diagnostic et la prise en charge en Réanimation de l’urosepsis communautaire et associé aux soins sont exposés en soulignant le problème des entérobactéries résistantes. Une conduite à tenir devant la survenue de bactériuries nosocomiales sur cathétérisme urinaire est proposée.

Objective: To assess the residual risk of waterborne contamination by Pseudomonas aeruginosa from a water network colonized by a single genotype [sequence type (ST) 299] despite the presence of antimicrobial filters in a medical intensive care unit (ICU). Methods: During the first 19-month period since the ICU opened, contamination of the water network was assessed monthly by collecting water upstream of the filters. Downstream water was also sampled to assess the efficiency of the filters. P. aeruginosa isolates from patients were collected and compared with the waterborne ST299 P. aeruginosa by multiplex-rep polymerase chain reaction (PCR), pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing. Cross-transmission events by other genotypes of P. aeruginosa were also assessed. Results: Overall, 1.3% of 449 samples of filtered water were positive for P. aeruginosa in inoculum, varying between 1 and 10 4 colony-forming units/100 mL according to the tap. All P. aeruginosa hydric isolates belonged to ST299 and displayed fewer than two single nucleotide polymorphisms (SNPs). Among 278 clinical isolates from 122 patients, 10 isolates in five patients showed identical profiles to the hydric ST299 clone on both multiplex-rep PCR and PFGE, and differed by an average of fewer than five SNPs, confirming the water network reservoir as the source of contamination by P. aeruginosa for 4.09% of patients. Cross -transmission events by other genotypes of P. aeruginosa were responsible for the contamination of 1.75% of patients. Discussion/conclusion: Antimicrobial filters are not sufficient to protect patients from waterborne pathogens when the water network is highly contaminated. A microbiological survey of filtered water may be needed in units hosting patients at risk of P. aeruginosa infections, even when all water points -of -use are fitted with filters. 2024 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

The aim of this study was to describe the characteristics of patients admitted to the intensive care unit with severe pneumonia due to SARS-CoV-2, comparing them according to successive waves, and to identify prognostic factors for morbidity and mortality. This single-center retrospective observational descriptive study was conducted from March 10, 2020, to October 17, 2021. All adult patients admitted with SARS-CoV-2 pneumonia presenting acute respiratory failure were included. COVID 19 diagnosis was confirmed by RT-PCR testing of respiratory specimens. The primary endpoint was ICU mortality. Secondary endpoints were the occurrence of ventilator-associated pneumonia (VAP) or bronchopulmonary aspergillosis. Over the study period, 437 patients were included of whom 282 (65

L'isavuconazole est un agent antifongique triazole de développement récent recommandé comme traitement de première ligne pour l'aspergillose pulmonaire invasive. Avec l'avènement de la pandémie de COVID-19, des cas d'aspergillose pulmonaire associée à la COVID-19 (CAPA) ont été décrits avec une prévalence allant de 5 à 30%. Nous avons développé et validé un modèle pharmacocinétique de population (PKpop) des concentrations plasmatiques d'isavuconazole chez les patients hospitalisés en unités de soins intensifs et réanimation atteints de CAPA La modélisation non linéaire à effets mixtes à l'aide du logiciel Monolix a été utilisé pour l'analyse pharmacocinétique de 65 concentrations plasmatiques minimales provenant de 18 patients. Les paramètres pharmacocinétiques ont été estimés au mieux avec un modèle à un compartiment. A partir du modèle validé des simulations de hautes posologies ont été évaluées par des simulations de Monte carlo. La moyenne des concentrations plasmatiques d'isavuconazole était de 1,87 [1,29-2,25] mg/L malgré une dose d'attaque prolongée (72 h pour un tiers des patients) et une dose d'entretien moyenne de 300 mg par jour. La modélisation pharmacocinétique a montré que le traitement d'épuration extra-rénal (EER) était significativement associé à une sous exposition, expliquant une partie de la variabilité de la clairance. Les simulations de Monte Carlo ont suggéré que le schéma posologique recommandé ne permettait pas d'atteindre la valeur minimale cible de 2 mg/L en temps voulu (72 h). Il s'agit du premier modèle pharmacocinétique populationnel sur l'isavuconazole développé pour les patients en soins intensifs atteints de CAPA, qui souligne la nécessité d'une surveillance thérapeutique de l'isavuconazole, notamment pour les patients sous EER. Aucun lien d'intérêt

BACKGROUND:A higher sodium (Na) dialysate concentration is recommended during renal replacement therapy (RRT) of acute kidney injury (AKI) to improve intradialytic hemodynamic tolerance, but it may lead to Na loading to the patient. We aimed to evaluate Na flux according to Na dialysate and infusate concentrations at 140 and 145 mmol/L during hemodialysis (HD) and hemodiafiltration (HDF).METHODS:Fourteen AKI patients that underwent consecutive HD or HDF sessions with Na dialysate/infusate at 140 and 145 mmol/L were included. Per-dialytic flux of Na was estimated using mean sodium logarithmic concentration including diffusive and convective influx. We compared the flux of sodium between HD140 and 145, and between HDF140 and 145.RESULTS:Nine HD140, ten HDF140, nine HD145, and 11 HDF145 sessions were analyzed. A Na gradient from the dialysate/replacement fluid to the patient was observed with dialysate/infusate Na at 145 mmol/L in both HD and HDF (p = 0.01). The comparison of HD145 to HD140 showed that higher Na dialysate induced a diffusive Na gradient to the patient (163 mmol vs. -25 mmol, p = 0.004) and that of HDF145 to -140 (211 vs. 36 mmol, p = 0.03) as well. Intradialytic hemodynamic tolerance was similar across all RRT sessions.CONCLUSIONS:During both HD and HDF, a substantial Na loading occurred with a Na dialysate and infusate at 145 mmol/L. This Na loading is smaller in HDF with Na dialysate and infusate concentration at 140 mmol/L and inversed with HD140. Clinical and intradialytic hemodynamic tolerance was fair regardless of Na dialysate and infusate.

OBJECTIVES:The use of extended intermittent infusion (EII) or continuous infusion (CI) of meropenem is recommended in intensive care unit (ICU) patients, but few data comparing these two options are available. This retrospective cohort study was conducted between 1 January 2019 and 31 March 2020 in a teaching hospital ICU. It aimed to determine the meropenem plasma concentrations achieved with CI and EII. METHODS:The study included septic patients treated with meropenem who had one or more meropenem plasma trough (Cmin) or steady-state concentration (Css) measurement(s), as appropriate. It then assessed the factors independently associated with attainment of the target concentration (Cmin or Css ≥ 10 mg/L) and the toxicity threshold (Cmin or Css ≥ 50 mg/L) using logistic regression models. RESULTS:Among the 70 patients analysed, the characteristics of those treated with EII (n = 33) and CI (n = 37) were balanced with the exception of estimates glomerular filtration rate (eGFR): median 30 mL/min/m2 (IQR 30, 84) vs. 79 mL/min/m2 (IQR 30, 124). Of the patients treated with EII, 21 (64%) achieved the target concentration, whereas 31 (97%) of those treated with CI achieved it (P < 0.001). Factors associated with target attainment were: CI (OR 16.28, 95% CI 2.05-407.5), daily dose ≥ 40 mg/kg (OR 12.23, 95% CI 1.76-197.0; P = 0.03) and eGFR (OR 0.98, 95% CI 0.97-0.99; P = 0.02). Attainment of toxicity threshold was associated with daily dose > 70 mg/kg (OR 35.5, 95% CI 5.61-410.3; P < 0.001). CONCLUSION:The results suggest the use of meropenem CI at 40-70 mg/kg/day, particularly in septic ICU patients with normal or augmented renal clearance.

Isavuconazole is a triazole antifungal agent recently recommended as first-line therapy for invasive pulmonary aspergillosis. With the COVID-19 pandemic, cases of COVID-19-associated pulmonary aspergillosis (CAPA) have been described with a prevalence ranging from 5 to 30%. We developed and validated a population pharmacokinetic (PKpop) model of isavuconazole plasma concentrations in intensive care unit patients with CAPA. Nonlinear mixed-effect modeling Monolix software were used for PK analysis of 65 plasma trough concentrations from 18 patients. PK parameters were best estimated with a one-compartment model. The mean of ISA plasma concentrations was 1.87 [1.29–2.25] mg/L despite prolonged loading dose (72 h for one-third) and a mean maintenance dose of 300 mg per day. Pharmacokinetics (PK) modeling showed that renal replacement therapy (RRT) was significantly associated with under exposure, explaining a part of clearance variability. The Monte Carlo simulations suggested that the recommended dosing regimen did not achieve the trough target of 2 mg/L in a timely manner (72 h). This is the first isavuconazole PKpop model developed for CAPA critical care patients underlying the need of therapeutic drug monitoring, especially for patients under RRT.

Background: In coronavirus disease 2019 (COVID-19) patients, increases in high-sensitive cardiac troponin T (hs-cTnT) have been reported to be associated with worse outcomes. In the critically ill, the prognostic value of hs-cTnT, however, remains to be assessed given that most previous studies have involved a case mix of non- and severely ill COVID-19 patients. Methods: We conducted, from March to May 2020, in three French intensive care units (ICUs), a multicenter retrospective cohort study to assess in-hospital mortality predictability of hs-cTnT levels in COVID-19 patients. Results: 111 laboratory-confirmed COVID-19 patients (68% of male, median age 67 (58–75) years old) were included. At ICU admission, the median Charlson Index, Simplified Acute Physiology Score II, and PaO2/FiO2 were at 3 (2–5), 37 (27–48), and 140 (98–154), respectively, and the median hs-cTnT serum levels were at 16.0 (10.1–31.9) ng/L. Seventy-five patients (68%) were mechanically ventilated, 41 (37%) were treated with norepinephrine, and 17 (15%) underwent renal replacement therapy. In-hospital mortality was 29% (32/111) and was independently associated with lower PaO2/FiO2 and higher hs-cTnT serum levels. Conclusions: At ICU admission, besides PaO2/FiO2, hs-cTnT levels may allow early risk stratification and triage in critically ill COVID-19 patients.

Background Precision medicine risk stratification is desperately needed to both avoid systemic antifungals treatment delay and over prescription in the critically ill with risk factors. The aim of the present study was to explore the combination of host immunoparalysis biomarker (monocyte human leukocyte antigen-DR expression (mHLA-DR)) and Candida sp wall biomarker β- d -glucan in risk stratifying patients for secondary invasive Candida infection (IC). Methods Prospective observational study. Two intensive care units (ICU). All consecutive non-immunocompromised septic shock patients. Serial blood samples ( n = 286) were collected at day 0, 2 and 7 and mHLA-DR and β- d -glucan were then retrospectively assayed after discharge. Secondary invasive Candida sp infection occurrence was then followed at clinicians’ discretion. Results Fifty patients were included, 42 (84%) had a Candida score equal or greater than 3 and 10 patients developed a secondary invasive Candida sp infection. ICU admission mHLA-DR expression and β- d -glucan (BDG) failed to predict secondary invasive Candida sp infection. Time-dependent cause-specific hazard ratio of IC was 6.56 [1.24–34.61] for mHLA-DR < 5000 Ab/c and 5.25 [0.47–58.9] for BDG > 350 pg/mL. Predictive negative value of mHLA-DR > 5000 Ab/c and BDG > 350 pg/mL combination at day 7 was 81% [95% CI 70–92]. Conclusions This study suggests that mHLA-DR may help predicting IC in high-risk patients with septic shock. The added value of BDG and other fungal tests should be regarded according to the host immune function markers.

Severe malaria accounts for approximately 10% of all cases of imported malaria in France; cases are mainly due to Plasmodium fakiparum, while other Plasmodium species are possible but uncommon (P. vivax, P. knowlesi, P. nzalariae, and P. ovate). On the basis of WHO criteria for endemic areas, the French criteria defining severe imported malaria in adults have been progressively adapted to the European healthcare level. Management of severe imported malaria is a diagnostic and treatment emergency and must be initially conducted in the intensive care unit. Anti-infective treatment is now based on intravenous artesunate, which must be available in every hospital of the country likely to receive severe imported malaria patients. Intravenous quinine is thus used as a second-line treatment and is restricted to limited indications. Critical care management of organ failure is essential, particularly in patients presenting with very severe malaria. To date, no adjunctive therapy (including exchange transfusion) has demonstrated clear beneficial effects. (C) 2018 Elsevier Masson SAS. All rights reserved.

Objectives: The use of a videolaryngoscope in the ICU on the first endotracheal intubation attempt and intubation-related complications is controversial. The objective of this study was to evaluate the first intubation attempt success rate in the ICU with the McGrath MAC videolaryngoscope (Medtronic, Minneapolis, MN) according to the operators' videolaryngoscope expertise and to describe its association with the occurrence of intubation-related complications. Design: Observational study. Setting: Medical ICU. Subjects: Consecutive endotracheal intubations in critically ill patients. Interventions: Systematic use of the videolaryngoscope. Measurements and Main Outcomes: We enrolled 202 consecutive endotracheal intubations. Overall first-attempt success rate was 126 of 202 (62%). Comorbidities, junior operator, cardiac arrest upon admission, and coma were associated with a lower first-attempt success rate. The first-attempt success rate was less than 50% in novice operators (1-5 previous experiences with videolaryngoscope, independently of airway expertise with direct laryngoscopies) and 87% in expert operators (> 15 previous experiences with videolaryngoscope). Multivariate analysis confirmed the association between specific skill training with videolaryngoscope and the first-attempt success rate. Severe hypoxemia and overall immediate intubation-related complications occurred more frequently in first-attempt failure intubations (24/76, 32%) than in first-attempt success intubations (14/126, 11%) (p< 0.001). Conclusions: We report for the first time in the critically ill that specific videolaryngoscopy skill training, assessed by the number of previous videolaryngoscopies performed, is an independent factor of first-attempt intubation success. Furthermore, we observed that specific skill training with the McGrath MAC videolaryngoscope was fast. Therefore, future trials evaluating videolaryngoscopy in ICUs should consider the specific skill training of operators in videolaryngoscopy.

Background : Precision medicine risk stratification is desperately needed to both avoid systemic antifungals treatment delay and over prescription in the critically ill with risk factors. The aim of the present study was to explore the combination of host immunoparalysis biomarker (monocyte human leukocyte antigen-DR expression (mHLA-DR)) and Candida sp wall biomarker β-d-glucan in risk stratifying patients for secondary invasive Candida infection (ICI). Methods : Prospective observational study. Two intensive care units (ICU). All consecutive non-immunocompromised septic shock patients. Serial blood samples (n=286) were collected at day 0, 2 and 7 and mHLA-DR and β-d-glucan were assayed. Secondary invasive Candida sp infection occurrence were then followed. Results : Fifty patients were included, 42 (84%) had a Candida score equal or greater than 3 and 10 patients developed a secondary invasive Candida sp infection. ICU admission mHLA-DR expression and β-d-glucan (BDG) failed to predict secondary invasive Candida sp infection. Time-dependent cause-specific hazard ratio of ICI was 6.56[1.24-34.61] for mHLA-DR < 5000 Ab/c and 5.25[0.47-58.9] for BDG > 350pg/mL. Predictive negative value of mHLA-DR > 5000 Ab/c and BDG > 350 pg/mL combination at day 7 was 81% [95%CI 70-92]. Conclusion : This proof of concept study suggests that mHLA-DR predicts ICI in high risk patients with septic shock. The added value of BDG and other fungal tests should be regarded according to the host immune function markers. Trial registration: ClinicalTrials.gov identifier: NCT03136081 Take home message : Combination of monocytic HLA-DR expression and beta-D-glucan in patients hospitalized for septic shock failed to predict invasive candida infection but could be useful to rule out infection.

Renal transplantation represents the best therapeutic option for end-stage renal failure and is widely performed. Recent advances in immunosuppressive drugs have improved the graft survival but has led to an increase in cardiovascular and infectious events. Severe complications that need intensive care have occurred in about 5% of renal transplant recipients. Reasons of admission are frequently acute respiratory failure and causes are mostly infectious. Acute kidney injury is common and may impact both short- and long-term graft functions. Current management should take into account the specificity of kidney transplant recipient and adverse effects of immunosuppression in order to improve the ICU mortality which remains above 30%.

La transplantation rénale est la thérapeutique de choix de l’insuffisance rénale chronique au stade ultime, son usage est de plus en plus large. Les progrès réalisés dans les traitements immunosuppresseurs ont permis une amélioration de la durée de vie du greffon, mais au prix d’une augmentation des complications cardiovasculaires et infectieuses. Environ 5 % des transplantés rénaux présentent des complications sévères qui nécessitent une prise en charge intensive. Elles sont principalement de cause infectieuse et dominées par la défaillance respiratoire aiguë. L’insuffisance rénale aiguë est commune, elle affecte la fonction du greffon à court et long termes. La prise en charge en réanimation de ces complications doit prendre en compte le terrain particulier du transplanté rénal et les effets délétères de l’immunosuppression, condition nécessaire à une amélioration de la mortalité qui reste à plus de 30 %.

Patients liberated from invasive mechanical ventilation are at risk of extubation failure, including inability to breathe without a tracheal tube (airway failure) or without mechanical ventilation (non-airway failure). We sought to identify respective risk factors for airway failure and non-airway failure following extubation.

En France, le paludisme grave d’importation concerne environ 12 a 14 % des acces palustres et implique tres majoritairement Plasmodium falciparum . A partir de la definition du paludisme grave de l’Organisation mondiale de la sante utilisee en zone d’endemie palustre, la definition francaise du paludisme grave d’importation de l’adulte a ete adaptee aux donnees et au contexte europeens. La prise en charge du paludisme grave est une urgence diagnostique et therapeutique qui doit etre realisee initialement en reanimation. Le traitement curatif du paludisme grave d’importation repose maintenant sur l’artesunate intraveineux (IV) qui doit etre disponible dans chaque hopital susceptible de recevoir ces patients. Des lors, la quinine IV devient un traitement de seconde ligne reserve a quelques circonstances. La prise en charge symptomatique des defaillances d’organes est primordiale, notamment au cours des formes les plus severes. Enfin, aucun traitement adjuvant n’a prouve, a ce jour, son efficacite en pratique clinique.

The members of the Palurea Study Group were provided in such a way that they could not be indexed as collaborators on PubMed. The publisher apologizes for this error and is pleased to list the members of the group here:

In France, severe imported malaria concerns around 12-14% of the malaria episodes, mainly due to Plasmodium falciparum. From the WHO definition of severe malaria in endemic areas, the French definition of severe imported malaria has been elaborated considering an European context. Severe malaria is a diagnostic and therapeutic emergency and the initial management must be conducted in intensive care unit. The curative treatment of severe malaria is based on intravenous artesunate, which now must be available everywhere in France. Consequently, intravenous quinine is a second line treatment, with some residual indications. Management of organ dysfunctions in intensive care unit remains crucial, particularly during the most severe forms of imported malaria. Currently, no adjunctive therapy has proved its effectiveness in clinical practice.