Fluid administration is one of the first lines of treatment for hemodynamic management of sepsis and septic shock. Studies investigating the effects of chloride-rich fluids including normal saline on ...renal function report controversial findings.
This is a prospective, observational, multicenter study. Patients with septic shock, defined according to Sepsis-2 definition, were eligible. A "high-dose" of chloride was defined as a chloride intake greater than 18 g administrated within the first 48 h of septic shock management. The purpose of this study was to investigate the impact of cumulative chloride infusion within the first 48 h of septic shock resuscitation on acute kidney injury (AKI).
Two hundred thirty-nine patients with septic shock were included. Patients who received a "high-dose" of chloride had significantly higher Sequential Organ Failure Assessment score at the time of enrolment (P < 0.001). Cumulative chloride load was higher in patients requiring renal replacement therapy (RRT) (31.1 vs. 25.2 g/48 h; P < 0.005). Propensity score-weighted regression did not find any association between "high-dose" of chloride and AKI requiring RRT (OR: 0.97 0.88-1.1; P = 0.69). There was no association between "high-dose" of chloride and worsening kidney function at H48 (OR: 0.94 0.83-1.1; P = 0.42). There was also no association between "high-dose" of chloride and ICU length of stay (P = 0.61), 28-day mortality (P = 0.83), or hospital mortality (P = 0.89).
At the early stage of resuscitation of critically ill patients with septic shock, administration of "high-dose" of chloride (> 18 g/48 h) was not associated with renal prognosis.
Background
The COVID-19 pandemic has highlighted the importance of intensive care units (ICUs) and their organization in healthcare systems. However, ICU capacity and availability are ongoing ...concerns beyond the pandemic, particularly due to an aging population and increasing complexity of care. This study aimed to assess the current and future shortage of ICU physicians in France, ten years after a previous evaluation. A national e-survey was conducted among French ICUs in January 2022 to collect data on ICU characteristics, medical staffing, individual physician characteristics, and education and training capacities.
Results
Among 290 ICUs contacted, 242 responded (response rate: 83%), representing 4943 ICU beds. The survey revealed an overall of 300 full time equivalent (FTE) ICU physician vacancies in the country. Nearly two-thirds of the participating ICUs reported at least one physician vacancy and 35% relied on traveling physicians to cover shifts. The ICUs most affected by physician vacancies were the ICUs of non-university affiliated public hospitals. The retirements expected in the next five years represented around 10% of the workforce. The median number of physicians per ICU was 7.0, corresponding to a ratio of 0.36 physician (FTE) per ICU bed. In addition, 27% of ICUs were at risk of critical dysfunction or closure due to vacancies and impending retirements.
Conclusion
The findings highlight the urgent need to address the shortage of ICU physicians in France. Compared to a similar study conducted in 2012, the inadequacy between ICU physician supply and demand has increased, resulting in a higher number of vacancies. Our study suggests that, among others, increasing the number of ICM residents trained each year could be a crucial step in addressing this issue. Failure to take appropriate measures may lead to further closures of ICUs and increased risks to patients in this healthcare system.
Background
Dexamethasone is recommended for COVID-19 patients who require oxygen therapy. However, its effectiveness in reducing mortality and intubation, and its safety, remain debated. We aimed to ...investigate whether dexamethasone reduces day-28 mortality in unselected patients with critical COVID-19.
Methods
We performed an observational cohort study in consecutive COVID-19 patients admitted to any of 13 French intensive care units (ICUs) in 2020. The primary objective was to determine whether early dexamethasone therapy was associated with day-28 mortality and the secondary objectives were to assess whether early dexamethasone decreased intubation requirements and to collect adverse events.
Results
Of 1058 included patients, 611 (57.75%) received early dexamethasone (early dexamethasone group), 358 (33.83%) did not receive any steroids (no steroids group), and 89 (8.41%) received late dexamethasone or other steroids. Day-28 mortality was similar between the early dexamethasone and the no steroids groups (15.06% and 14.25%, respectively;
P
= 0.59). Factors associated with day-28 mortality were older age (adjusted hazard ratio aHR, 1.06; 1.04–1.09;
P
< 0.001), worse SOFA score (aHR, 1.13; 1.06–1.20;
P
< 0.001), and immunocompromised status (aHR, 1.59; 1.01–2.50;
P
= 0.043). Early dexamethasone was associated with fewer intubations (48.55% vs. 61.49%,
P
< 0.001) and more ventilator-free days by day 28 (22 2–28 vs. 17 1–28 days,
P
= 0.003), compared to no steroids. Ventilator-associated pneumonia (VAP) was more common with early dexamethasone (HR, 1.29 1.01–1.63,
P
= 0.04) than with no steroids, whereas no differences were noted for bloodstream infection, fungal infection, or gastrointestinal bleeding.
Conclusions
Early dexamethasone in critically ill COVID-19 patients was not associated with lower day-28 mortality. However, early dexamethasone was associated with lower intubation needs and more ventilator-free days by day 28. In patients treated with invasive mechanical ventilation, early dexamethasone was associated with a higher risk of VAP.
Key messages
What is already known on this topic
Dexamethasone decreased day-28 mortality in the randomised controlled trial RECOVERY in patients admitted for COVID-19, including 74% who required oxygen and 16% invasive mechanical ventilation (iMV). Other trials targeting critically ill patients did not replicate this finding, leaving uncertainty about the benefits of dexamethasone.
What this study adds
In our large observational cohort of critically ill COVID-19 patients, of whom 61% required iMV, early systemic dexamethasone was not associated with lower day-28 mortality compared to no steroids. However, early dexamethasone was associated with less need for iMV, more days alive and off iMV, and a higher frequency of ventilator-associated pneumonia in the iMV sub-group.
How this study might affect research, practice, or policy
This study suggests that early dexamethasone may be warranted in critically ill COVID-19 patients, provided those receiving iMV are monitored closely for ventilatory-associated pneumonia.
Introduction:
Necrotizing fasciitis represents a life-threatening infectious condition that causes spreading necrotisis of superficial fascia and subcutaneous cellular tissues. We describe the case ...of a patient diagnosed with septic and toxic shocks leading to multiple organ failure successfully treated with a combination of extracorporeal life support, continuous renal replacement therapy, and a hemoadsorption device.
Methods:
A 41-year-old patient presented with necrotizing fasciitis and multi-organ failure. Initial extracorporeal life support therapy was implanted, compensating for systolic failure. Due to acute renal failure that persisted in time, continuous renal replacement therapy was added. Despite these treatments and as a last attempt to control the septic condition, a CytoSorb® hemoadsorption device was installed in parallel to the extracorporeal life support circuit and two sessions were run.
Results:
During the days following CytoSorb® treatment, hemodynamic stabilization was observed, as well as normalization of lactic acidosis and blood parameters.
Conclusion:
This case describes the successful use of CytoSorb® with continuous renal replacement therapy and extracorporeal life support in a combined way to overcome a critical phase of septic shock in a young adult patient. This combination of treatments turned out to be efficient for this patient in the context of necrotizing fasciitis.
Abstract Introduction The objective of the study to is to determine the characteristics associated with endotracheal intubation in septic shock patients. Methods This is a post hoc analysis of the ...database of the SEPSISPAM study, including patients with septic shock. Results Among the 776 patients, 633 (82%) were intubated within 12 hours of study inclusion (early intubation), 113 (15%) were never intubated, and 30 (4%) had delayed intubation. Intensive care units (ICUs) were classified according to frequency of early intubation: early intubation less than 80% of patients (lowest frequency: 7 ICUs, 254 patients), 80% to 90% (middle frequency: 5 ICUs, 170 patients), and greater than 90% (highest frequency: 6 ICUs, 297 patients). Type of ICU, pulmonary infection, lactate greater than 2 mmol/L, lower Pa o2 /fraction of inspired oxygen ratio, lower Glasgow score, and absence of immunosuppression were independently associated with early intubation. Patients never intubated had a lower initial severity and a low mortality rate. In comparison to patients intubated early, patients with delayed intubation had had fewer days alive without organ support by day 28. Intensive care units with the highest frequency of early intubation had a higher mortality rate in comparison to ICUs with middle frequency of early intubation. A nonsignificant increased mortality was observed in ICU with lowest frequency of early intubation. Conclusions Practices regarding the place of endotracheal intubation in septic shock may impact outcome.
Abstract
Rationale
Early corticosteroid treatment is used to treat COVID-19-related acute respiratory distress syndrome (ARDS). Infection is a well-documented adverse effect of corticosteroid ...therapy.
Objectives
To determine whether early corticosteroid therapy to treat COVID-19 ARDS was associated with ventilator-associated pneumonia (VAP).
Methods
We retrospectively included adults with COVID-19-ARDS requiring invasive mechanical ventilation (MV) for ≥ 48 h at any of 15 intensive care units in 2020. We divided the patients into two groups based on whether they did or did not receive corticosteroids within 24 h. The primary outcome was VAP incidence, with death and extubation as competing events. Secondary outcomes were day 90-mortality, MV duration, other organ dysfunctions, and VAP characteristics.
Measurements and main results
Of 670 patients (mean age, 65 years), 369 did and 301 did not receive early corticosteroids. The cumulative VAP incidence was higher with early corticosteroids (adjusted hazard ratio aHR 1.29; 95% confidence interval 95% CI 1.05–1.58;
P
= 0.016). Antibiotic resistance of VAP bacteria was not different between the two groups (odds ratio 0.94, 95% CI 0.58–1.53;
P
= 0.81). 90-day mortality was 30.9% with and 24.3% without early corticosteroids, a nonsignificant difference after adjustment on age, SOFA score, and VAP occurrence (aHR 1.15; 95% CI 0.83–1.60;
P
= 0.411). VAP was associated with higher 90-day mortality (aHR 1.86; 95% CI 1.33–2.61;
P
= 0.0003).
Conclusions
Early corticosteroid treatment was associated with VAP in patients with COVID-19-ARDS. Although VAP was associated with higher 90-day mortality, early corticosteroid treatment was not. Longitudinal randomized controlled trials of early corticosteroids in COVID-19-ARDS requiring MV are warranted.
Activation of the TREM-1 pathway is associated with outcome in life threatening COVID-19. Data suggest that modulation of this pathway with nangibotide, a TREM-1 modulator may improve survival in ...TREM-1 activated patients (identified using the biomarker sTREM-1).
Phase 2 double-blind randomized controlled trial assessing efficacy, safety, and optimum treatment population of nangibotide (1.0 mg/kg/h) compared to placebo. Patients aged 18–75 years were eligible within 7 days of SARS-CoV-2 documentation and within 48 h of the onset of invasive or non-invasive respiratory support because of COVID-19-related ARDS. Patients were included from September 2020 to April 2022, with a pause in recruitment between January and August 2021. Primary outcome was the improvement in clinical status defined by a seven-point ordinal scale in the overall population with a planned sensitivity analysis in the subgroup of patients with a sTREM-1 level above the median value at baseline (high sTREM-1 group). Secondary endpoints included safety and all-cause 28-day and day 60 mortality. The study was registered in EudraCT (2020-001504-42) and ClinicalTrials.gov (NCT04429334).
The study was stopped after 220 patients had been recruited. Of them, 219 were included in the mITT analysis. Nangibotide therapy was associated with an improved clinical status at day 28. Fifty-two (52.0%) of patients had improved in the placebo group compared to 77 (64.7%) of the nangibotide treated population, an odds ratio (95% CI) for improvement of 1.79 (1.02–3.14), p = 0.043. In the high sTREM-1 population, 18 (32.7%) of placebo patients had improved by day 28 compared to 26 (48.1%) of treated patients, an odds ratio (95% CI) of 2.17 (0.96–4.90), p = 0.063 was observed. In the overall population, 28 (28.0%) of placebo treated patients were not alive at the day 28 visit compared to 19 (16.0%) of nangibotide treated patients, an absolute improvement (95% CI) in all-cause mortality at day 28, adjusted for baseline clinical status of 12.1% (1.18–23.05). In the high sTREM-1 population (n = 109), 23 (41.8%) of patients in the placebo group and 12 (22.2%) of patients in the nangibotide group were not alive at day 28, an adjusted absolute reduction in mortality of 19.9% (2.78–36.98). The rate of treatment emergent adverse events was similar in both placebo and nangibotide treated patients.
Whilst the study was stopped early due to low recruitment rate, the ESSENTIAL study demonstrated that TREM-1 modulation with nangibotide is safe in COVID-19, and results in a consistent pattern of improved clinical status and mortality compared to placebo. The relationship between sTREM-1 and both risk of death and treatment response merits further evaluation of nangibotide using precision medicine approaches in life threatening viral pneumonitis.
The study was sponsored by Inotrem SA.
According to French regulation, the study was approved by the Angers University Hospital ethics committee and information letters were sent to the patients. To the best of our knowledge, our cohort ...is the first specific report of late cannulation experience in this indication and our results suggest that it is feasible and may have benefit some patients (69% survival rate in patients under 60 years of age cannulated after 7 days of mechanical ventilation in our cohort). ...a late initiation of VV-ECMO for CARDS was not associated with an increased mortality in our cohort.
Background
Recent studies identified coronavirus disease 2019 (COVID-19) as a risk factor for invasive pulmonary aspergillosis (IPA) but produced conflicting data on IPA incidence and impact on ...patient outcomes. We aimed to determine the incidence and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) in mechanically ventilated patients.
Methods
We performed a multicenter retrospective observational cohort study in consecutive adults admitted to 15 French intensive care units (ICUs) in 2020 for COVID-19 requiring mechanical ventilation. CAPA was diagnosed and graded according to 2020 ECMM/ISHAM consensus criteria. The primary objective was to determine the incidence of proven/probable CAPA, and the secondary objectives were to identify risk factors for proven/probable CAPA and to assess associations between proven/probable CAPA and patient outcomes.
Results
The 708 included patients (522 73.7% men) had a mean age of 65.2 ± 10.8 years, a median mechanical ventilation duration of 15.0 8.0–27.0 days, and a day-90 mortality rate of 28.5%. Underlying immunosuppression was present in 113 (16.0%) patients. Corticosteroids were used in 348 (63.1%) patients. Criteria for probable CAPA were met by 18 (2.5%) patients; no patient had histologically proven CAPA. Older age was the only factor significantly associated with probable CAPA (hazard ratio HR, 1.04; 95% CI 1.00–1.09;
P
= 0.04). Probable CAPA was associated with significantly higher day-90 mortality (HR, 2.07; 95% CI 1.32–3.25;
P
= 0.001) but not with longer mechanical ventilation or ICU length of stay.
Conclusion
Probable CAPA is a rare but serious complication of severe COVID-19 requiring mechanical ventilation and is associated with higher day-90 mortality.
Graphical Abstract
Despite the benefits of mechanical ventilation, its use in critically ill patients is associated with complications and had led to the growth of noninvasive techniques. We assessed the effect of ...early intubation (first 8 h after vasopressor start) in septic shock patients, as compared to non-early intubated subjects (unexposed), regarding in-hospital mortality, intensive care and hospital length of stay.
This study involves secondary analysis of a multicenter prospective study. To adjust for baseline differences in potential confounders, propensity score matching was carried out. In-hospital mortality was analyzed in a time-to-event fashion, while length of stay was assessed as a median difference using bootstrapping.
A total of 735 patients (137 intubated in the first 8 h) were evaluated. Propensity score matching identified 78 pairs with similar severity and characteristics on admission. Intubation was used in all patients in the early intubation group and in 27 (35%) subjects beyond 8 h in the unexposed group. Mortality occurred in 35 (45%) and in 26 (33%) subjects in the early intubation and unexposed groups (hazard ratio 1.44 95% CI 0.86-2.39, p = 0.16). ICU and hospital length of stay were not different among groups 9 vs. 5 (95% CI 1 to 7) and 14 vs. 16 (95% CI - 7 to 8) days. All sensitivity analyses confirmed the robustness of our findings.
An early approach to invasive mechanical ventilation did not improve outcomes in this matched cohort of patients. The limited number of patients included in these analyses out the total number included in the study may limit generalizability of these findings. Trial registration NCT02780466. Registered on May 19, 2016.
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