Cytokine removal in human septic shock : where are we and where are we going?

Although improving, the mortality from septic shock still remains high despite increased international awareness. As a consequence, much effort has focused on alternative treatment strategies in an effort to improve outcomes. The application of blood purification therapies to improve immune homeostasis has been suggested as one such method, but these approaches, such as high-volume continuous haemofiltration or cytokine and/or endotoxin removal, have enjoyed little success to date. More recently, the use of sorbent technologies has attracted much attention. These adsorbers are highly effective at removing inflammatory mediators, in particular, cytokines, from the bloodstream. This narrative review is the executive summary of meetings held throughout the 6th International Fluid Academy Days in Antwerp, Belgium (Nov 23-25, 2017), focusing on the current understanding regarding the use of such adsorbers in humans with septic shock. We followed a modified Delphi approach involving a combination of evidence appraisal together with expert opinion in order to achieve recommendations for practice and, importantly, future research

High mean arterial pressure target to improve sepsis-associated acute kidney injury in patients with prior hypertension: a feasibility study

Background : The optimal mean arterial pressure (MAP) in cases of septic shock is still a matter of debate in patients with prior hypertension. An MAP between 75 and 85 mmHg can improve glomerular filtration rate (GFR) but its effect on tubular function is unknown. We assessed the effects of high MAP level on glomerular and tubular renal function in two intensive care units of a teaching hospital. Inclusion criteria were patients with a history of chronic hypertension and developing AKI in the first 24 h of septic shock. Data were collected during two 6 h periods of MAP regimen administered consecutively after haemodynamic stabilisation in an order depending on the patient's admission unit: a high-target period (80–85 mmHg) and a low-target period (65–70 mmHg). The primary endpoint was the creatinine clearance (CrCl) calculated from urine and serum samples at the end of each MAP period by the UV/P formula. Results : 26 patients were included. Higher urine output (+0.2 (95%:0, 0.4) mL/kg/h; P = 0.04), urine sodium (+6 (95% CI 0.2, 13) mmol/L; P = 0.04) and lower serum creatinine (− 10 (95% CI − 17, − 3) µmol/L; P = 0.03) were observed during the high-MAP period as compared to the low-MAP period, resulting in a higher CrCl (+25 (95% CI 11, 39) mL/mn; P = 0.002). The urine creatinine, urine–plasma creatinine ratio, urine osmolality, fractional excretion of sodium and urea showed no significant variation. The KDIGO stage at inclusion only interacted with serum creatinine variation and low level of sodium excretion at inclusion did not interact with these results. Conclusions : In the early stage of sepsis-associated AKI, a high-MAP target in patients with a history of hypertension was associated with a higher CrCl, but did not affect the kidneys' ability to concentrate urine, which may reflect no effect on tubular function

Characterization of acute kidney injury in critically ill patients with severe coronavirus disease 2019

Abstract Background Coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) frequency, severity and characterization in critically ill patients has not been reported. Methods Single-centre cohort performed from 3 March 2020 to 14 April 2020 in four intensive care units in Bordeaux University Hospital, France. All patients with COVID-19 and pulmonary severity criteria were included. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A systematic urinary analysis was performed. The incidence, severity, clinical presentation, biological characterization (transient versus persistent AKI; proteinuria, haematuria and glycosuria) and short-term outcomes were evaluated. Results Seventy-one patients were included, with basal serum creatinine (SCr) of 69 ± 21 µmol/L. At admission, AKI was present in 8/71 (11%) patients. Median [interquartile range (IQR)] follow-up was 17 (12–23) days. AKI developed in a total of 57/71 (80%) patients, with 35% Stage 1, 35% Stage 2 and 30% Stage 3 AKI; 10/57 (18%) required renal replacement therapy (RRT). Transient AKI was present in only 4/55 (7%) patients and persistent AKI was observed in 51/55 (93%). Patients with persistent AKI developed a median (IQR) urine protein/creatinine of 82 (54–140) (mg/mmol) with an albuminuria/proteinuria ratio of 0.23 ± 20, indicating predominant tubulointerstitial injury. Only two (4%) patients had glycosuria. At Day 7 after onset of AKI, six (11%) patients remained dependent on RRT, nine (16%) had SCr >200 µmol/L and four (7%) had died. Day 7 and Day 14 renal recovery occurred in 28% and 52%, respectively. Conclusion Severe COVID-19-associated AKI is frequent, persistent, severe and characterized by an almost exclusive tubulointerstitial injury without glycosuria

Continuation vs Discontinuation of Renin-Angiotensin System Inhibitors Before Major Noncardiac Surgery

ImportanceBefore surgery, the best strategy for managing patients who are taking renin-angiotensin system inhibitors (RASIs) (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) is unknown. The lack of evidence leads to conflicting guidelines.ObjectiveTo evaluate whether a continuation strategy vs a discontinuation strategy of RASIs before major noncardiac surgery results in decreased complications at 28 days after surgery.Design, setting, and participantsRandomized clinical trial that included patients who were being treated with a RASI for at least 3 months and were scheduled to undergo a major noncardiac surgery between January 2018 and April 2023 at 40 hospitals in France.InterventionPatients were randomized to continue use of RASIs (n = 1107) until the day of surgery or to discontinue use of RASIs 48 hours prior to surgery (ie, they would take the last dose 3 days before surgery) (n = 1115).Main outcomes and measuresThe primary outcome was a composite of all-cause mortality and major postoperative complications within 28 days after surgery. The key secondary outcomes were episodes of hypotension during surgery, acute kidney injury, postoperative organ failure, and length of stay in the hospital and intensive care unit during the 28 days after surgery.ResultsOf the 2222 patients (mean age, 67 years [SD, 10 years]; 65% were male), 46% were being treated with angiotensin-converting enzyme inhibitors at baseline and 54% were being treated with angiotensin receptor blockers. The rate of all-cause mortality and major postoperative complications was 22% (245 of 1115 patients) in the RASI discontinuation group and 22% (247 of 1107 patients) in the RASI continuation group (risk ratio, 1.02 [95% CI, 0.87-1.19]; P = .85). Episodes of hypotension during surgery occurred in 41% of the patients in the RASI discontinuation group and in 54% of the patients in the RASI continuation group (risk ratio, 1.31 [95% CI, 1.19-1.44]). There were no other differences in the trial outcomes.Conclusions and relevanceAmong patients who underwent major noncardiac surgery, a continuation strategy of RASIs before surgery was not associated with a higher rate of postoperative complications than a discontinuation strategy.Trial registrationClinicalTrials.gov Identifier: NCT03374449

Renal replacement therapy in acute kidney injury: controversy and consensus

Renal replacement therapies (RRTs) represent a cornerstone in the management of severe acute kidney injury. This area of intensive care and nephrology has undergone significant improvement and evolution in recent years. Continuous RRTs have been a major focus of new technological and treatment strategies. RRT is being used increasingly in the intensive care unit, not only for renal indications but also for other organ-supportive strategies. Several aspects related to RRT are now well established, but others remain controversial. In this review, we review the available RRT modalities, covering technical and clinical aspects. We discuss several controversial issues, provide some practical recommendations, and where possible suggest a research agenda for the future

Dysphosphorémie des patients de réanimation traités par hémofiltration (apport des nouvelles solutions supplémentées)

INTRODUCTION : Les patients en choc septique ont très souvent une défaillance rénale associée qui nécessite le recours à l'épuration extra-rénale. Plusieurs niveaux de volume de traitement sont proposés par plusieurs auteurs, sans que le niveau optimal clairement soit déterminé. Les troubles hydro-électrolytiques secondaires à l'hémofilttration sont l'hypokaliémie et l'hypophosphorémie. Les principales conséquences de l'hypophosphorémie sont une altération des fonctions cardiaques, diaphragmatiques, et neurologiques. L'arrivée sur le marché d'un nouveau liquide de substitution, le Phoxilium®, permettrait-il d'améliorer l'homéostasie phosphocalcique ? PATIENTS ET METHODES : L'objectif principal de cette étude est de déterminer l'incidence des dysphosphorémies induites par l'épuration extra-rénale des patients en choc septique, chez qui on utilisait historiquement des solutions dde substitution dépourvues en phosphore. Nous avons donc étudié prospectivement, le comportement de la phosphorémie et de la calcémie chez trois groupes de patients : le premier groupe de 20 patients a été hémofiltré avec un haut volume de traitement avec des liquides de substitution dépourvus en phosphore, le deuxième groupe de 22 patients a été hémofiltré avec un très haut volume de traitement avec des liquides de substitution dépourvus en phosphore, le troisième de 12 patients a été hémofiltré avec un haut volume de traitement et un liquide de substitution supplémenté, le Phoxilium®. RESULTATS : Parmi les patients du groupe haut débit, 70 % d'entre eux feront au moins un épisode d'hypophosphorémie (phosphore < 0.8 mmol/L), et 20 % feront au moins un épisode d'hyphosphorémie sévère (phosphore < 0.32 mmol/L). Parmi les patients du groupe très haut débit, ils feront tous au moins un épisode d'hypophosphorémie, et 31 % feront au moins un épisode d'hypophosphorémie sévère. Parmi les patients du groupe Phoxilium®, 16 % d'entre eux feront au moins un épisode d'hypophosphorémie, et aucun ne fera d'épisode d'hypophosphorémie sévère. Concernant l'étude de la calcémie, 69 % des patients du groupe haut débit et 67 % du groupe très haut débit feront un épisode d'hypercalcémie. CONCLUSION : Cette étude démontre l'intérêt important qu'apporte le Phoxillium® dans le maintien de l'homéostasie du bilan phosphocalcique du patient hémofiltré en choc septique.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Déficit acquis en antithrombine et rôle de sa supplémentation chez les patients septiques sous hémofiltration veino veineuse continue

BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF