The viral epidemic caused by the new Coronavirus SARS-CoV-2 is responsible for the new Coronavirus disease-2019 (Covid-19). Fifteen percent of the Covid-19 patients will require hospital stay, and ...10% of them will need urgent respiratory and hemodynamic support in the intensive care unit (ICU). Covid-19 is an infectious disease characterized by inflammatory syndrome, itself leading to reduced food intake and increased muscle catabolism. Therefore Covid-19 patients are at high risk of being malnourished, making the prevention of malnutrition and the nutritional management key aspects of care. Urgent, brutal and massive arrivals of patients needing urgent respiratory care and artificial ventilation lead to the necessity to reorganize hospital care, wards and staff. In that context, nutritional screening and care may not be considered a priority. Moreover, at the start of the epidemic, due to mask and other protecting material shortage, the risk of healthcare givers contamination have led to not using enteral nutrition, although indicated, because nasogastric tube insertion is an aerosol-generating procedure. Clinical nutrition practice based on the international guidelines should therefore adapt and the use of degraded procedures could unfortunately be the only way. Based on the experience from the first weeks of the epidemic in France, we emphasize ten challenges for clinical nutrition practice. The objective is to bring objective answers to the most frequently met issues to help the clinical nutrition caregivers to promote nutritional care in the hospitalized Covid-19 patient. We propose a flow chart for optimizing the nutrition management of the Covid-19 patients in the non-ICU wards.
Purpose
Sepsis-induced immunosuppression is postulated to contribute to a heightened risk of nosocomial infection (NI). This prospective, single-center, observational study was conducted to assess ...whether low monocyte human leukocyte antigen-DR expression (mHLA-DR), proposed as a global biomarker of sepsis immunosuppression, was associated with an increased incidence of NI after septic shock.
Methods
The study included 209 septic shock patients. mHLA-DR was measured by flow cytometry at days (D) 3–4 and 6–9 after the onset of shock. After septic shock, patients were screened daily for NI at four sites (microbiologically documented pulmonary, urinary tract, bloodstream, and catheter-related infections). A competing risk approach was used to evaluate the impact of low mHLA-DR on the incidence of NI.
Results
At D3–4, we obtained measurements in 153 patients. Non-survivors (
n
= 51) exhibited lower mHLA-DR values expressed as means of fluorescence intensities than survivors (
n
= 102) (33 vs. 67;
p
< 0.001). The patients who developed NI (
n
= 37) exhibited lower mHLA-DR values than those without NI (
n
= 116) (39 vs. 65;
p
= 0.008). mHLA-DR ≤54 remained independently associated with NI occurrence after adjustment for clinical parameters (gender, simplified acute physiology score II, sepsis-related organ failure assessment, intubation, and central venous catheterization) with an adjusted hazards ratio (aHR) of 2.52 (95% CI 1.20–5.30);
p
= 0.02. Similarly, at D6–9, low mHLA-DR (≤57) remained independently associated with NI with an aHR of 2.18 (95% CI 1.04–4.59);
p
= 0.04.
Conclusions
In septic shock patients, after adjustment with usual clinical confounders (including ventilation and central venous catheterization), persistent low mHLA-DR expression remained independently associated with the development of secondary NI.
Prone position is used in acute respiratory distress syndrome and in coronavirus disease 2019 acute respiratory distress syndrome. However, it is unclear how responders may be identified and whether ...an oxygenation response improves outcome. The objective of this study was to quantify the response to prone position, describe the differences between coronavirus disease 2019 acute respiratory distress syndrome and acute respiratory distress syndrome, and explore variables associated with survival.
Retrospective, observational, multicenter, international cohort study.
Seven ICUs in Italy, United Kingdom, and France.
Three hundred seventy-six adults (220 coronavirus disease 2019 acute respiratory distress syndrome and 156 acute respiratory distress syndrome).
None.
Preproning, a greater proportion of coronavirus disease 2019 acute respiratory distress syndrome patients had severe disease (53% vs 40%), worse Pao2/Fio2 (13.0 kPa interquartile range, 10.5-15.5 kPa vs 14.1 kPa interquartile range, 10.5-18.6 kPa; p = 0.017) but greater compliance (38 mL/cm H2O interquartile range, 27-53 mL/cm H2O vs 31 mL/cm H2O interquartile range, 21-37 mL/cm H2O; p < 0.001). Patients with coronavirus disease 2019 acute respiratory distress syndrome had a longer median time from intubation to prone position (2.0 d interquartile range, 0.7-5.0 d vs 1.0 d interquartile range, 0.5-2.9 d; p = 0.03). The proportion of responders, defined by an increase in Pao2/Fio2 greater than or equal to 2.67 kPa (20 mm Hg), upon proning, was similar between acute respiratory distress syndrome and coronavirus disease 2019 acute respiratory distress syndrome (79% vs 76%; p = 0.5). Responders had earlier prone position (1.4 d interquartile range, 0.7-4.2 d vs 2.5 d interquartile range, 0.8-6.2 d; p = 0.06). Prone position less than 24 hours from intubation achieved greater improvement in oxygenation (11 kPa interquartile range, 4-21 kPa vs 7 kPa interquartile range, 2-13 kPa; p = 0.002). The variables independently associated with the "responder" category were Pao2/Fio2 preproning (odds ratio, 0.89 kPa-1 95% CI, 0.85-0.93 kPa-1; p < 0.001) and interval between intubation and proning (odds ratio, 0.94 d-1 95% CI, 0.89-0.99 d-1; p = 0.019). The overall mortality was 45%, with no significant difference observed between acute respiratory distress syndrome and coronavirus disease 2019 acute respiratory distress syndrome. Variables independently associated with mortality included age (odds ratio, 1.03 yr-1 95% CI, 1.01-1.05 yr-1; p < 0.001); interval between hospital admission and proning (odds ratio, 1.04 d-1 95% CI, 1.002-1.084 d-1; p = 0.047); and change in Pao2/Fio2 on proning (odds ratio, 0.97 kPa-1 95% CI, 0.95-0.99 kPa-1; p = 0.002).
Prone position, particularly when delivered early, achieved a significant oxygenation response in ~80% of coronavirus disease 2019 acute respiratory distress syndrome, similar to acute respiratory distress syndrome. This response was independently associated with improved survival.
The immediate overwhelming release of inflammatory mediators in septic shock is rapidly followed by strong anti-inflammatory responses inducing a state of immunosuppression. The patients who survive ...the initial hyper-inflammatory step of septic shock but subsequently die may be those who do not recover from immunosuppression. We assessed whether a low monocyte human leukocyte antigen-DR (mHLA-DR) expression, proposed as a marker of immunosuppression, is an independent predictor of mortality in patients who survived the initial 48 h of septic shock.
Prospective observational study performed in two adult intensive care units at a university hospital.
93 consecutive patients with septic shock.
At days 1-2, mHLA-DR values (determined by flow cytometry) were not significantly different between survivors and non-survivors. A sharp difference became highly significant at days 3-4 when survivors had increased their values, while non-survivors had not (43% vs. 18%, percentage of HLA-DR positive monocyte, p < 0.001). Multivariate logistic regression analysis revealed that low mHLA-DR (< 30%) at days 3-4 remained independently associated with mortality after adjustment for usual clinical confounders, adjusted odds ratio (CI): 6.48 (95% CI: 1.62-25.93).
The present preliminary results show that mHLA-DR is an independent predictor of mortality in septic shock patients. Being a marker of immune failure, low mHLA-DR may provide a rationale for initiating therapy to reverse immunosuppression. After validation of the current results in multicenter studies, mHLA-DR may help to stratify patients when designing a mediator-directed therapy in a time-dependent manner.
Delaying renal replacement therapy (RRT) for some time in critically ill patients with severe acute kidney injury and no severe complication is safe and allows optimisation of the use of medical ...devices. Major uncertainty remains concerning the duration for which RRT can be postponed without risk. Our aim was to test the hypothesis that a more-delayed initiation strategy would result in more RRT-free days, compared with a delayed strategy.
This was an unmasked, multicentre, prospective, open-label, randomised, controlled trial done in 39 intensive care units in France. We monitored critically ill patients with severe acute kidney injury (defined as Kidney Disease: Improving Global Outcomes stage 3) until they had oliguria for more than 72 h or a blood urea nitrogen concentration higher than 112 mg/dL. Patients were then randomly assigned (1:1) to either a strategy (delayed strategy) in which RRT was started just after randomisation or to a more-delayed strategy. With the more-delayed strategy, RRT initiation was postponed until mandatory indication (noticeable hyperkalaemia or metabolic acidosis or pulmonary oedema) or until blood urea nitrogen concentration reached 140 mg/dL. The primary outcome was the number of days alive and free of RRT between randomisation and day 28 and was done in the intention-to-treat population. The study is registered with ClinicalTrial.gov, NCT03396757 and is completed.
Between May 7, 2018, and Oct 11, 2019, of 5336 patients assessed, 278 patients underwent randomisation; 137 were assigned to the delayed strategy and 141 to the more-delayed strategy. The number of complications potentially related to acute kidney injury or to RRT were similar between groups. The median number of RRT-free days was 12 days (IQR 0–25) in the delayed strategy and 10 days (IQR 0–24) in the more-delayed strategy (p=0·93). In a multivariable analysis, the hazard ratio for death at 60 days was 1·65 (95% CI 1·09–2·50, p=0·018) with the more-delayed versus the delayed strategy. The number of complications potentially related to acute kidney injury or renal replacement therapy did not differ between groups.
In severe acute kidney injury patients with oliguria for more than 72 h or blood urea nitrogen concentration higher than 112 mg/dL and no severe complication that would mandate immediate RRT, longer postponing of RRT initiation did not confer additional benefit and was associated with potential harm.
Programme Hospitalier de Recherche Clinique.
Purpose
Sepsis syndrome represents the leading cause of death in intensive care unit. Patients present features consistent with a decline in immune responsiveness potentially contributing to ...mortality. We investigated whether CD4
+
CD25
+
regulatory T cells (Treg) participate in the induction of lymphocyte anergy after sepsis.
Method
Observational study in septic shock patients and experimental study in mice.
Results
We took advantage of the recently described flow cytometric gating strategy using the measurement of CD25 and CD127 expressions for monitoring Treg (CD4
+
CD25
+
CD127
−
Foxp3
+
). In patients the increased circulating Treg percentage significantly correlated with a decreased lympho-proliferative response. In a murine model of sepsis mimicking these observations, the ex vivo downregulation of Foxp3 expression using siRNA was associated with a restoration of this response.
Conclusion
The relative increase in circulating Treg might play a role in lymphocyte anergy described after septic shock and represent a standardizable surrogate marker of declining proliferative capacity after sepsis.
Acute kidney injury (AKI) requiring renal replacement therapy (RRT) is a serious complication in the ICU that results in increased mortality and risk of chronic kidney disease (CKD). Some studies ...suggest RRT modality may have an impact on long-term renal recovery after AKI. However, other predictive factors of severe long-term CKD in ICU patients with AKI requiring RRT are unknown.
We performed an ancillary study of the multicenter ELVIS trial in the population with AKI requiring RRT. Patients alive 3 months after RRT initiation were eligible. Serum creatinine levels available at 3, 6 and 12 months and 3 and 5 years were recorded. CKD stage was determined according to the glomerular filtration rate as estimated by the CKD-EPI formula. At each timepoint, two groups of patients were compared, a no/mild CKD group with normal or mildly to moderately decreased renal function (stages 1, 2 and 3 of the international classification) and a severe CKD group (stages 4 and 5). Our objective was to identify predictive factors of severe long-term CKD.
Of the 287 eligible patients, 183 had follow-up at 3 months, 136 (74.3%) from the no/mild CKD group and 47 (25.7%) from the severe CKD group, and 122 patients at 5 years comprising 96 (78.7%) from the no/mild CKD group and 26 (21.3%) from the severe CKD group. Multivariate analysis showed that a long RRT period was associated with severe CKD up to 12 months (OR
= 1.03 95% CI 1.02-1.05 per day) and that a high SOFA score at the initiation of RRT was not associated with severe CKD up to 5 years (OR
= 0.85 95% CI 0.77-0.93 per point).
Severe long-term CKD was found in 21% of ICU survivors who underwent RRT for AKI. The duration of the RRT in AKI patients was identified as a new predictive factor for severe long-term CKD. This finding should be taken into consideration in future studies on the prognosis of ICU patients with AKI requiring RRT. Trial registration ELVIS trial was registered with ClinicalTrials.gov, number: NCT00875069 (June 16, 2014), and this ancillary study was registered with ClinicalTrials.gov, number: NCT03302624 (October 6, 2017).
Sepsis syndrome represents the leading cause of death in intensive care unit. Patients present features consistent with a decline in immune responsiveness potentially contributing to mortality. We ...investigated whether CD4(+)CD25(+) regulatory T cells (Treg) participate in the induction of lymphocyte anergy after sepsis.
Observational study in septic shock patients and experimental study in mice.
We took advantage of the recently described flow cytometric gating strategy using the measurement of CD25 and CD127 expressions for monitoring Treg (CD4(+)CD25(+)CD127(-)Foxp3(+)). In patients the increased circulating Treg percentage significantly correlated with a decreased lympho-proliferative response. In a murine model of sepsis mimicking these observations, the ex vivo downregulation of Foxp3 expression using siRNA was associated with a restoration of this response.
The relative increase in circulating Treg might play a role in lymphocyte anergy described after septic shock and represent a standardizable surrogate marker of declining proliferative capacity after sepsis.
Purpose
Improvements in survival after septic shock will most likely rely on our capacity to manage individualized therapies based on the measurement of rapidly accessible biomarkers. As the early ...phase of septic shock is dominated by severe alterations of the cardiovascular system, the predictive value for mortality of pro-vasopressin (pro-AVP) and pro-adrenomedullin (pro-ADM), two vasoactive pro-hormones, was assessed.
Methods
In 99 consecutive patients, pro-hormone concentrations were measured (immunoluminometric assay) three times within the first week after the onset of septic shock.
Results
Pro-AVP and pro-ADM concentrations were significantly increased in non-survivors in comparison with survivors and were significantly associated with mortality after both univariate and multivariate analysis. Importantly, when assessed as a pair, pro-ADM and pro-AVP were even more informative.
Conclusions
Both Pro-ADM and pro-AVP appear to be good biomarkers for the prediction of 28-day mortality after septic shock. However, their association in a single variable tends to improve their predictive capacity.
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