Clinical review: Blood purification for sepsis

Sepsis is the primary cause of death in the intensive care unit. Extracorporeal blood purification therapies have been proposed for patients with sepsis in order to improve outcomes since these therapies can alter the host inflammatory response by non-selective removal of inflammatory mediators or bacterial products or both. Recent technological progress has increased the number of techniques available for blood purification and their performance. In this overview, we report on the latest advances in blood purification for sepsis and how they relate to current concepts of disease, and we review the current evidence for high-volume hemofiltration, cascade hemofiltration, hemoadsorption, coupled plasma filtration adsorption, high-adsorption hemofiltration, and high-cutoff hemofiltration/hemodialysis. Promising results have been reported with all of these blood purification therapies, showing that they are well tolerated, effective in clearing inflammatory mediators or bacterial toxins (or both) from the plasma, and efficacious for improvement of various physiologic outcomes (for example, hemodynamics and oxygenation). However, numerous questions, including the timing, duration, and frequency of these therapies in the clinical setting, remain unanswered. Large multicenter trials evaluating the ability of these therapies to improve clinical outcomes (that is, mortality or organ failure), rather than surrogate markers such as plasma mediator clearance or transient improvement in physiologic variables, are required to define the precise role of blood purification in the management of sepsis

Intraoperative carcinoid syndrome during small-bowel neuroendocrine tumour surgery

Only few descriptions of intraoperative carcinoid syndrome (ioCS) have been reported. The primary objective of this study was to describe ioCS. A second aim was to identify risk factors of ioCS. We retrospectively analysed patients operated for small-bowel neuroendocrine tumour in our institution between 2007 and 2015, and receiving our preventive local regimen of octreotide continuous administration. ioCS was defined as highly probable in case of rapid (<5 min) arterial blood pressure changes ≥40%, not explained by surgical/anaesthetic management and regressive ≥20% after octreotide bolus injection. Probable cases were ioCS which did not meet all criteria of highly-probable ioCS. Suspected ioCS were detected on the anaesthesia record by an injection of octreotide due to a manifestation which did not meet the criteria for highly-probable or probable ioCS. A total of 81 patients (liver metastases: 59, prior carcinoid syndrome: 49, carcinoid heart disease: 7) were included; 139 ioCS occurred in 45 patients: 45 highly probable, 67 probable and 27 suspected. ioCs was hypertensive (91%) and/or hypotensive (29%). There was no factor, including the use of vasopressors, significantly associated with the occurrence of an ioCS. All surgeries were completed and one patient died from cardiac failure 4 days after surgery. After preoperative octreotide continuous infusion, ioCS were mainly hypertensive. No ioCS risk factors, including vasopressor use, were identified. No intraoperative carcinoid crisis occurred, suggesting the clinical relevance of a standardized octreotide prophylaxis protocol

Low-dose hydrocortisone reduces norepinephrine duration in severe burn patients: a randomized clinical trial

INTRODUCTION: The aim of this study was to assess the effect of low-dose corticosteroid therapy in reducing shock duration after severe burn. METHODS: A placebo-controlled, double-blind, randomized clinical trial (RCT) was performed on two parallel groups in the burn intensive care unit (ICU). Patients were randomized to receive either low-dose corticosteroid therapy or placebo for seven days. A corticotropin test was performed at the time of randomization, before the administration of the treatment dose. Thirty-two severely burned patients with refractory shock (>0.5 μg/kg/min of norepinephrine) were prospectively included in the study. RESULTS: We included 12 patients in the hydrocortisone-treated group and 15 patients in the placebo group in the final analysis. Among these patients, 21 were nonresponders to the corticotropin test. Median norepinephrine treatment duration (primary objective) was significantly lower in the corticosteroid-treated versus the placebo group (57 hours versus 120 hours, P = 0.035). The number of patients without norepinephrine 72 hours after inclusion was significantly lower in the treated group (P = 0.003, log-rank test analysis). The total quantities of norepinephrine administered to patients were lower in the hydrocortisone-treated versus the placebo group (1,205 μg/kg (1,079 to 2,167) versus 1,971 μg/kg (1,535 to 3,893), P = 0.067). There was no difference in terms of ICU or hospital length of stay, sepsis incidence, cicatrization or mortality. CONCLUSIONS: In this placebo-controlled, randomized, double-blind clinical trial, we show for the first time that the administration of low-dose hydrocortisone in burn patients with severe shock reduces vasopressor administration. TRIAL REGISTRATION: Clinicaltrial.gov NCT00149123. Registered 6 September 2005. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0740-0) contains supplementary material, which is available to authorized users

Source of Circulating Pentraxin 3 in Septic Shock Patients

Sepsis, which is the leading cause of death in intensive care units (ICU), has been acknowledged as a global health priority by the WHO in 2017. Identification of biomarkers allowing early stratification and recognition of patients at higher risk of death is crucial. One promising biomarker candidate is pentraxin-3 (PTX3); initially elevated and persistently increased plasma concentration in septic patients has been associated with increased mortality. PTX3 is an acute phase protein mainly stored in neutrophil granules. These cells are responsible for rapid and prompt release of PTX3 in inflammatory context, but the cellular origin responsible for successive days' elevation in sepsis remains unknown. Upon inflammatory stimulation, PTX3 can also be produced by other cell types, including endothelial and immune cells. As in septic patients immune alterations have been described, we therefore sought to investigate whether such cells participated in the elevation of PTX3 over the first days after septic shock onset. To address this point, PTX3 was measured in plasma from septic shock patients at day 3 after ICU admission as well as in healthy volunteers (HV), and the capacity of whole blood cells to secrete PTX3 after inflammatory stimulation was evaluated ex vivo. A significantly mean higher (100-fold) concentration of plasma PTX3 was found in patients compared to HV, which was likely due to the inflammation-induced initial release of the pre-existing PTX3 reservoir contained in neutrophils. Strikingly, when whole blood was stimulated ex vivo with LPS no significant difference between patients and HV in PTX3 release was found. This was in contrast with TNFα which decreased production was illustrative of the endotoxin tolerance phenomenon occurring in septic patients. Then, the release of PTX3 protein from a HV neutrophil-free PBMC endotoxin tolerance model was investigated. At the transcriptional level, PTX3 seems to be a weakly tolerizable gene similar to TNFα. Conversely, increased protein levels observed in anergy condition reflects a non-tolerizable phenotype, more likely to an anti-inflammatory marker. Hence, altered immune cells still have the ability to produce PTX3 in response to an inflammatory trigger, and therefore circulating white blood cell subset could be responsible of the sustained PTX3 plasma levels over the first days of sepsis setting

Change in Sleep Quality of Residents the Night Before High-Fidelity Simulation: Results From a Prospective 1-Year National Survey.

peer reviewed[en] OBJECTIVE: The stress level of participants in high-fidelity simulation stems from various factors but may result in anticipatory anxiety causing sleep disturbances during the night prior to simulation. The objective of this survey was to determine the change in sleep quality of residents during the night prior to the simulation. METHODS: The survey was proposed for 1 year to all residents at the beginning of the simulation, in 10 simulation centres. The questionnaire combined demographics and the Leeds Sleep Evaluation Questionnaire using visual analogue scales divided into 4 sleep qualitative domains. The primary outcome was the prevalence of sleep disturbance (>10 mm on 1 domain). Secondary outcomes were the prevalence of severe sleep disturbance (>25 mm), as well as qualitatively and quantitatively reported explanatory sleep parameters. RESULTS: Among respondents, 66% [95% CI: 63 to 69] of residents had more than 10 mm and 27% [95% CI: 24 to 30] had more than 25 mm of sleep disturbance. Residents with a sleep disturbance of more than 10 mm had fewer hours of sleep (6.4 [standard deviation=1.8] vs 7.3 [standard deviation=1.3], difference: -0.9 [95% CI: -1.1 to -0.7]; P < .0001), with a higher number of night-time awakenings (1.3 [standard deviation=1.5] vs 0.7 [standard deviation=0.9], difference: 0.6 [95% CI: 0.4 to 0.8]; P < .0001). CONCLUSION: Among residents participating in the simulation, a high prevalence of change in sleep quality during the night before the simulation was noted. Strategies to help residents achieve better sleep prior to simulation should be explored

Publisher Correction:COVID-19-associated acute kidney injury: consensus report of the 25^th Acute Disease Quality Initiative (ADQI) Workgroup (Nature Reviews Nephrology, (2020), 10.1038/s41581-020-00356-5)

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Endogenous Retroviruses Transcriptional Modulation After Severe Infection, Trauma and Burn

Although human endogenous retroviruses (HERVs) expression is a growing subject of interest, no study focused before on specific endogenous retroviruses loci activation in severely injured patients. Yet, HERV reactivation is observed in immunity compromised settings like some cancers and auto-immune diseases. Our objective was to assess the transcriptional modulation of HERVs in burn, trauma and septic shock patients. We analyzed HERV transcriptome with microarray data from whole blood samples of a burn cohort (n = 30), a trauma cohort (n = 105) and 2 septic shock cohorts (n = 28, n = 51), and healthy volunteers (HV, n = 60). We described expression of the 337 probesets targeting HERV from U133 plus 2.0 microarray in each dataset and then we compared HERVs transcriptional modulation of patients compared to healthy volunteers. Although all 4 cohorts contained critically ill patients, the majority of the 337 HERVs was not expressed (around 74% in mean). Each cohort had differentially expressed probesets in patients compared to HV (from 19 to 46). Strikingly, 5 HERVs were in common in all types of severely injured patients, with 4 being up-modulated in patients. We highlighted co-expressed profiles between HERV and nearby CD55 and CD300LF genes as well as autonomous HERV expression. We suggest an inflammatory-specific HERV transcriptional response, and importantly, we introduce that the HERVs close to immunity-related genes might have a role on its expression

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]