Comparison of renal histopathology and gene expression profiles between severe COVID-19 and bacterial sepsis in critically ill patients

 

Comparison of renal histopathology and gene expression profiles between severe COVID-19 and bacterial sepsis in critically ill patients

 

by Meint Volbeda, Daniela Jou-Valencia, Marius C. van den Heuvel, Marjolein Knoester, Peter J. Zwiers, Janesh Pillay, Stefan P. Berger, Peter H. J. van der Voort, Jan G. Zijlstra, Matijs van Meurs and Jill Moser 

 

Critical Care volume 25, Article number: 202 (2021) 

 

Background

The mechanisms driving acute kidney injury (AKI) in critically ill COVID-19 patients are unclear. We collected kidney biopsies from COVID-19 AKI patients within 30 min after death in order to examine the histopathology and perform mRNA expression analysis of genes associated with renal injury.

Methods

This study involved histopathology and mRNA analyses of postmortem kidney biopsies collected from patients with COVID-19 (n = 6) and bacterial sepsis (n = 27). Normal control renal tissue was obtained from patients undergoing total nephrectomy (n = 12). The mean length of ICU admission-to-biopsy was 30 days for COVID-19 and 3–4 days for bacterial sepsis patients.

Results

We did not detect SARS-CoV-2 RNA in kidney biopsies from COVID-19-AKI patients yet lung tissue from the same patients was PCR positive. Extensive acute tubular necrosis (ATN) and peritubular thrombi were distinct histopathology features of COVID-19-AKI compared to bacterial sepsis-AKI. ACE2 mRNA levels in both COVID-19 (fold change 0.42, p = 0.0002) and bacterial sepsis patients (fold change 0.24, p < 0.0001) were low compared to control. The mRNA levels of injury markers NGAL and KIM-1 were unaltered compared to control tissue but increased in sepsis-AKI patients. Markers for inflammation and endothelial activation were unaltered in COVID-19 suggesting a lack of renal inflammation. Renal mRNA levels of endothelial integrity markers CD31, PV-1 and VE-Cadherin did not differ from control individuals yet were increased in bacterial sepsis patients (CD31 fold change 2.3, p = 0.0006, PV-1 fold change 1.5, p = 0.008). Angiopoietin-1 mRNA levels were downregulated in renal tissue from both COVID-19 (fold change 0.27, p < 0.0001) and bacterial sepsis patients (fold change 0.67, p < 0.0001) compared to controls. Moreover, low Tie2 mRNA expression (fold change 0.33, p = 0.037) and a disturbed VEGFR2/VEGFR3 ratio (fold change 0.09, p < 0.0001) suggest decreased microvascular flow in COVID-19.

Conclusions

In a small cohort of postmortem kidney biopsies from COVID-19 patients, we observed distinct histopathological and gene expression profiles between COVID-19-AKI and bacterial sepsis-AKI. COVID-19 was associated with more severe ATN and microvascular thrombosis coupled with decreased microvascular flow, yet minimal inflammation. Further studies are required to determine whether these observations are a result of true pathophysiological differences or related to the timing of biopsy after disease onset.

Effect of intra-arrest trans-nasal evaporative cooling in out-of-hospital cardiac arrest: a pooled individual participant data analysis

 

Effect of intra-arrest trans-nasal evaporative cooling in out-of-hospital cardiac arrest: a pooled individual participant data analysis

 

by Fabio Silvio Taccone, Jacob Hollenberg, Sune Forsberg, Anatolij Truhlar, Martin Jonsson, Filippo Annoni, Dan Gryth, Mattias Ringh, Jerome Cuny, Hans-Jörg Busch, Jean-Louis Vincent, Leif Svensson and Per Nordberg 

 

Critical Care volume 25, Article number: 198 (2021)

 

Background

Randomized trials have shown that trans-nasal evaporative cooling initiated during CPR (i.e. intra-arrest) effectively lower core body temperature in out-of-hospital cardiac arrest patients. However, these trials may have been underpowered to detect significant differences in neurologic outcome, especially in patients with initial shockable rhythm.

Methods

We conducted a post hoc pooled analysis of individual data from two randomized trials including 851 patients who eventually received the allocated intervention and with available outcome (“as-treated” analysis). Primary outcome was survival with favourable neurological outcome at hospital discharge (Cerebral Performance Category [CPC] of 1–2) according to the initial rhythm (shockable vs. non-shockable). Secondary outcomes included complete neurological recovery (CPC 1) at hospital discharge.

Results

Among the 325 patients with initial shockable rhythms, favourable neurological outcome was observed in 54/158 (34.2%) patients in the intervention and 40/167 (24.0%) in the control group (RR 1.43 [confidence intervals, CIs 1.01–2.02]). Complete neurological recovery was observed in 40/158 (25.3%) in the intervention and 27/167 (16.2%) in the control group (RR 1.57 [CIs 1.01–2.42]). Among the 526 patients with initial non-shockable rhythms, favourable neurological outcome was in 10/259 (3.8%) in the intervention and 13/267 (4.9%) in the control group (RR 0.88 [CIs 0.52–1.29]; p = 0.67); survival and complete neurological recovery were also similar between groups. No significant benefit was observed for the intervention in the entire population.

Conclusions

In this pooled analysis of individual data, intra-arrest cooling was associated with a significant increase in favourable neurological outcome in out-of-hospital cardiac arrest patients with initial shockable rhythms. Future studies are needed to confirm the potential benefits of this intervention in this subgroup of patients.

Unmatched ventilation and perfusion measured by electrical impedance tomography predicts the outcome of ARDS

 

Unmatched ventilation and perfusion measured by electrical impedance tomography predicts the outcome of ARDS

 

by Elena Spinelli, Michael Kircher, Birgit Stender, Irene Ottaviani, Maria C. Basile, Ines Marongiu, Giulia Colussi, Giacomo Grasselli, Antonio Pesenti and Tommaso Mauri 

 

Critical Care volume 25, Article number: 192 (2021)

 

Background

In acute respiratory distress syndrome (ARDS), non-ventilated perfused regions coexist with non-perfused ventilated regions within lungs. The number of unmatched regions might reflect ARDS severity and affect the risk of ventilation-induced lung injury. Despite pathophysiological relevance, unmatched ventilation and perfusion are not routinely assessed at the bedside. The aims of this study were to quantify unmatched ventilation and perfusion at the bedside by electrical impedance tomography (EIT) investigating their association with mortality in patients with ARDS and to explore the effects of positive end-expiratory pressure (PEEP) on unmatched ventilation and perfusion in subgroups of patients with different ARDS severity based on PaO2/FiO2 and compliance.

Methods

Prospective observational study in 50 patients with mild (36%), moderate (46%), and severe (18%) ARDS under clinical ventilation settings. EIT was applied to measure the regional distribution of ventilation and perfusion using central venous bolus of saline 5% during end-inspiratory pause. We defined unmatched units as the percentage of only ventilated units plus the percentage of only perfused units.

Results

Percentage of unmatched units was significantly higher in non-survivors compared to survivors (32[27–47]% vs. 21[17–27]%, p < 0.001). Percentage of unmatched units was an independent predictor of mortality (OR 1.22, 95% CI 1.07–1.39, p = 0.004) with an area under the ROC curve of 0.88 (95% CI 0.79–0.97, p < 0.001). The percentage of ventilation to the ventral region of the lung was higher than the percentage of ventilation to the dorsal region (32 [27–38]% vs. 18 [13–21]%, p < 0.001), while the opposite was true for perfusion (28 [22–38]% vs. 36 [32–44]%, p < 0.001).

Higher percentage of only perfused units was correlated with lower dorsal ventilation (r =  − 0.486, p < 0.001) and with lower PaO2/FiO2 ratio (r =  − 0.293, p = 0.039).

Conclusions

EIT allows bedside assessment of unmatched ventilation and perfusion in mechanically ventilated patients with ARDS. Measurement of unmatched units could identify patients at higher risk of death and could guide personalized treatment.

Why and how to open intensive care units to family visits during the pandemic

 

Why and how to open intensive care units to family visits during the pandemic

 

by Giovanni Mistraletti, Alberto Giannini, Giuseppe Gristina, Paolo Malacarne, Davide Mazzon, Elisabetta Cerutti, Alessandro Galazzi, Ilaria Giubbilo, Marco Vergano, Vladimiro Zagrebelsky, Luigi Riccioni, Giacomo Grasselli, Silvia Scelsi, Maurizio Cecconi and Flavia Petrini 

 

Critical Care volume 25, Article number: 191 (2021) 

 

Since the lockdown because of the pandemic, family members have been prohibited from visiting their loved ones in hospital. While it is clearly complicated to implement protocols for the admission of family members, we believe precise strategic goals are essential and operational guidance is needed on how to achieve them. Even during the pandemic, we consider it a priority to share strategies adapted to every local setting to allow family members to enter intensive care units and all the other hospital wards.

Effects of early extubation followed by noninvasive ventilation versus standard extubation on the duration of invasive mechanical ventilation in hypoxemic non-hypercapnic patients: a systematic review and individual patient data meta-analysis of randomized controlled trials

 

Effects of early extubation followed by noninvasive ventilation versus standard extubation on the duration of invasive mechanical ventilation in hypoxemic non-hypercapnic patients: a systematic review and individual patient data meta-analysis of randomized controlled trials

 

by Rosanna Vaschetto, Alessandro Pecere, Gavin D. Perkins, Dipesh Mistry, Gianmaria Cammarota, Federico Longhini, Miguel Ferrer, Renata Pletsch-Assunção, Michele Carron, Francesca Moretto, Haibo Qiu, Francesco Della Corte, Francesco Barone-Adesi and Paolo Navalesi

 

Critical Care volume 25, Article number: 189 (2021) 

 

Background

Usefulness of noninvasive ventilation (NIV) in weaning patients with non-hypercapnic hypoxemic acute respiratory failure (hARF) is unclear. The study aims to assess in patients with non-hypercapnic hARF, the efficacy of NIV after early extubation, compared to standard weaning.

Methods

In this individual patient data meta-analysis, we searched EMBASE, Medline and Cochrane Central Register of Controlled Trials to identify potentially eligible randomized controlled trials published from database inception to October 2020. To be eligible, studies had to include patients treated with NIV after early extubation and compared to conventional weaning in adult non-hypercapnic hARF patients. Anonymized individual patient data from eligible studies were provided by study investigators. Using one-step and two-step meta-analysis models we tested the difference in total days spent on invasive ventilation.

Results

We screened 1605 records. Six studies were included in quantitative synthesis. Overall, 459 participants (mean [SD] age, 62 [15] years; 269 [59%] males) recovering from hARF were included in the analysis (233 in the intervention group and 226 controls). Participants receiving NIV had a shorter duration of invasive mechanical ventilation compared to control group (mean difference, − 3.43; 95% CI − 5.17 to − 1.69 days, p < 0.001), a shorter duration of total days spent on mechanical ventilation (mean difference, − 2.04; 95% CI − 3.82 to − 0.27 days, p = 0.024), a reduced risk of ventilatory associated pneumonia (odds ratio, 0.24; 95% CI 0.08 to 0.71, p = 0.014), a reduction of time spent in ICU (time ratio, 0.81; 95% CI 0.68 to 0.96, p = 0.015) and in-hospital (time ratio, 0.81; 95% CI 0.69 to 0.95, p = 0.010), with no difference in ICU mortality.

Conclusions

Although primary studies are limited, using an individual patient data metanalysis approach, NIV after early extubation appears useful in reducing total days spent on invasive mechanical ventilation.

 

Acute kidney injury in SARS-CoV2-related pneumonia ICU patients: a retrospective multicenter study

 

Acute kidney injury in SARS-CoV2-related pneumonia ICU patients: a retrospective multicenter study

 

by Guillaume Geri, Michael Darmon, Lara Zafrani, Muriel Fartoukh, Guillaume Voiriot, Julien Le Marec, Saafa Nemlaghi, Antoine Vieillard-Baron and Elie Azoulay 

 

Annals of Intensive Care volume 11, Article number: 86 (2021) 

 

Background

While acute kidney injury (AKI) is frequent in severe SARS-CoV2-related pneumonia ICU patients, few data are still available about its risk factors.

Methods

Retrospective observational study performed in four university affiliated hospitals in Paris. AKI was defined according to the KIDGO guidelines. Factors associated with AKI were picked up using multivariable mixed-effects logistic regression. Independent risk factors of day 28 mortality were assessed using Cox model.

Results

379 patients (median age 62 [53,69], 77% of male) were included. Half of the patients had AKI (n = 195, 52%) including 58 patients (15%) with AKI stage 1, 44 patients (12%) with AKI stage 2, and 93 patients (25% with AKI stage 3). Chronic kidney disease (OR 7.41; 95% CI 2.98–18.4), need for invasive mechanical ventilation at day 1 (OR 4.83; 95% CI 2.26–10.3), need for vasopressors at day 1 (OR 2.1; 95% CI 1.05–4.21) were associated with increased risk of AKI. Day 28 mortality in the cohort was 26.4% and was higher in patients with AKI (37.4 vs. 14.7%, P < 0.001). Neither AKI (HR 1.35; 95% CI 0.78–2.32) nor AKI stage were associated with mortality (HR [95% CI] for stage 1, 2 and 3 when compared to no AKI of, respectively, 1.02 [0.49–2.10], 1.73 [0.81–3.68] and 1.42 [0.78–2.58]).

Conclusion

In this large cohort of SARS-CoV2-related pneumonia patients admitted to the ICU, AKI was frequent, mostly driven by preexisting chronic kidney disease and life sustaining therapies, with unclear adjusted relationship with day 28 outcome.

Accuracy of pancreatic stone protein for the diagnosis of infection in hospitalized adults: a systematic review and individual patient level meta-analysis

 

Accuracy of pancreatic stone protein for the diagnosis of infection in hospitalized adults: a systematic review and individual patient level meta-analysis

 

by Josef Prazak, Irina Irincheeva, Martin J. Llewelyn, Daiana Stolz, Luis García de Guadiana Romualdo, Rolf Graf, Theresia Reding, Holger J. Klein, Philippe Eggimann and Yok-Ai Que 

 

Critical Care volume 25, Article number: 182 (2021)

 

Background

Accurate biomarkers to diagnose infection are lacking. Studies reported good performance of pancreatic stone protein (PSP) to detect infection. The objective of the study was to determine the performance of PSP in diagnosing infection across hospitalized patients and calculate a threshold value for that purpose.

Methods

A systematic search across Cochrane Central Register of Controlled Trials and MEDLINE databases (1966–March 2019) for studies on PSP published in English using ‘pancreatic stone protein’, ‘PSP’, ‘regenerative protein’, ‘lithostatin’ combined with ‘infection’ and ‘sepsis’ found 44 records. The search was restricted to the five trials that evaluated PSP for the initial detection of infection in hospitalized adults. Individual patient data were obtained from the investigators of all eligible trials. Data quality and validity was assessed according to PRISMA guidelines. We choose a fixed-effect model to calculate the PSP cut-off value that best discriminates infected from non-infected patients.

Results

Infection was confirmed in 371 of 631 patients. The median (IQR) PSP value of infected versus uninfected patients was 81.5 (30.0–237.5) versus 19.2 (12.6–33.57) ng/ml, compared to 150 (82.70–229.55) versus 58.25 (15.85–120) mg/l for C-reactive protein (CRP) and 0.9 (0.29–4.4) versus 0.15 (0.08–0.5) ng/ml for procalcitonin (PCT). Using a PSP cut-off of 44.18 ng/ml, the ROC AUC to detect infection was 0.81 (0.78–0.85) with a sensitivity of 0.66 (0.61–0.71), specificity of 0.83 (0.78–0.88), PPV of 0.85 (0.81–0.89) and NPV of 0.63 (0.58–0.68). When a model combining PSP and CRP was used, the ROC AUC improved to 0.90 (0.87–0.92) with higher sensitivity 0.81 (0.77–0.85) and specificity 0.84 (0.79–0.90) for discriminating infection from non-infection. Adding PCT did not improve the performance further.

Conclusions

PSP is a promising biomarker to diagnose infections in hospitalized patients. Using a cut-off value of 44.18 ng/ml, PSP performs better than CRP or PCT across the considered studies. The combination of PSP with CRP further enhances its accuracy.

Impact of Blood Product Transfusions on the Risk of ICU-Acquired Infections in Septic Shock*

 

Impact of Blood Product Transfusions on the Risk of ICU-Acquired Infections in Septic Shock*

 

by Péju, Edwige; Llitjos, Jean-François; Charpentier, Julien; François, Anne; Marin, Nathalie; Cariou, Alain; Chiche, Jean-Daniel; Mira, Jean-Paul; Lambert, Jérôme; Jamme, Matthieu; Pène, Frédéric 

Critical Care Medicine: June 2021 - Volume 49 - Issue 6 - p 912-922

OBJECTIVES: 

Transfusions of blood products are common in critically ill patients and have a potential for immunomodulation. The aim of this study is to address the impact of transfusion of blood products on the susceptibility to ICU-acquired infections in the high-risk patients with septic shock.

DESIGN: 

A single-center retrospective study over a 10-year period (2008–2017).

SETTING: 

A medical ICU of a tertiary-care center.

PATIENTS: 

All consecutive patients diagnosed for septic shock within the first 48 hours of ICU admission were included. Patients who were discharged or died within the first 48 hours were excluded.

INTERVENTIONS: 

RBC, platelet, and fresh frozen plasma transfusions collected up to 24 hours prior to the onset of ICU-acquired infection.

MEASUREMENTS AND MAIN RESULTS: 

During the study period, 1,152 patients were admitted for septic shock, with 893 patients remaining alive in the ICU after 48 hours of management. A first episode of ICU-acquired infection occurred in 28.3% of the 48-hour survivors, with a predominance of pulmonary infections (57%). Patients with ICU-acquired infections were more likely to have received RBC, platelet, and fresh frozen plasma transfusions. In a multivariate Cox cause-specific analysis, transfusions of platelets (cause-specific hazard ratio = 1.55 [1.09–2.20]; p = 0.01) and fresh frozen plasma (cause-specific hazard ratio = 1.38 [0.98–1.92]; p = 0.05) were independently associated with the further occurrence of ICU-acquired infections.

CONCLUSIONS: 

Transfusions of platelets and fresh frozen plasma account for risk factors of ICU-acquired infections in patients recovering from septic shock. The occurrence of ICU-acquired infections should be considered as a relevant endpoint in future studies addressing the indications of transfusions in critically ill patients.

Checklist for Early Recognition and Treatment of Acute Illness and Injury: An Exploratory Multicenter International Quality-Improvement Study in the ICUs With Variable Resources

 

Checklist for Early Recognition and Treatment of Acute Illness and Injury: An Exploratory Multicenter International Quality-Improvement Study in the ICUs With Variable Resources

 

 

by Vukoja, Marija MD, PhD1,2; Dong, Yue MD3; Adhikari, Neill K. J. MDCM, MSc4–6; Schultz, Marcus J. MD, PhD7–10; Arabi, Yaseen M. MD11; Martin-Loeches, Ignacio MD, PhD12–14; Hache, Manuel MD15; Gavrilovic, Srdjan MD1,2; Kashyap, Rahul MB BS, MBA3; Gajic, Ognjen MD, MSc16; for the Checklist for Early Recognition and Treatment of Acute Illness and Injury (CERTAIN) Investigators of the SCCM Discovery Network Checklist for Early Recognition and Treatment of Acute Illness and Injury (CERTAIN)

 

Critical Care Medicine: June 2021 - Volume 49 - Issue 6 - p e598-e612

 

 

OBJECTIVES: 

To determine whether the “Checklist for Early Recognition and Treatment of Acute Illness and Injury” decision support tool during ICU admission and rounding is associated with improvements in nonadherence to evidence-based daily care processes and outcomes in variably resourced ICUs.

DESIGN, SETTINGS, PATIENTS: 

This before-after study was performed in 34 ICUs (15 countries) from 2013 to 2017. Data were collected for 3 months before and 6 months after Checklist for Early Recognition and Treatment of Acute Illness and Injury implementation.

INTERVENTIONS: 

Checklist for Early Recognition and Treatment of Acute Illness and Injury implementation using remote simulation training.

MEASUREMENTS AND MAIN RESULTS: 

The coprimary outcomes, modified from the original protocol before data analysis, were nonadherence to 10 basic care processes and ICU and hospital length of stay. There were 1,447 patients in the preimplementation phase and 2,809 patients in the postimplementation phase. After adjusting for center effect, Checklist for Early Recognition and Treatment of Acute Illness and Injury implementation was associated with reduced nonadherence to care processes (adjusted incidence rate ratio [95% CI]): deep vein thrombosis prophylaxis (0.74 [0.68–0.81), peptic ulcer prophylaxis (0.46 [0.38–0.57]), spontaneous breathing trial (0.81 [0.76–0.86]), family conferences (0.86 [0.81–0.92]), and daily assessment for the need of central venous catheters (0.85 [0.81–0.90]), urinary catheters (0.84 [0.80–0.88]), antimicrobials (0.66 [0.62–0.71]), and sedation (0.62 [0.57–0.67]). Analyses adjusted for baseline characteristics showed associations of Checklist for Early Recognition and Treatment of Acute Illness and Injury implementation with decreased ICU length of stay (adjusted ratio of geometric means [95% CI]) 0.86 [0.80–0.92]), hospital length of stay (0.92 [0.85–0.97]), and hospital mortality (adjusted odds ratio [95% CI], 0.81 (0.69–0.95).

CONCLUSIONS: 

A quality-improvement intervention with remote simulation training to implement a decision support tool was associated with decreased nonadherence to daily care processes, shorter length of stay, and decreased mortality.

The impact of right ventricular injury on the mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis

The impact of right ventricular injury on the mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis

by Ryota Sato, Siddharth Dugar, Wisit Cheungpasitporn, Mary Schleicher, Patrick Collier, Saraschandra Vallabhajosyula and Abhijit Duggal 

Critical Care volume 25, Article number: 172 (2021)

Background

Previous studies have found various incidences of right ventricular (RV) injury and its association with clinical outcome in patients with acute respiratory distress syndrome (ARDS). In this systematic review and meta-analysis, we aimed to investigate the impact of the presence of RV injury on mortality in patients with ARDS.

Method

We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials for studies investigating the association between RV injury and mortality. Two authors independently evaluated whether studies meet eligibility criteria and extracted the selected patients’ and studies’ characteristics and outcomes. RV injury was diagnosed by trans-thoracic echocardiogram (TTE), trans-esophageal echocardiogram (TEE) and PAC (pulmonary artery catheter) in the included studies. The primary outcome was the association between mortality and the presence of RV injury in patients with ARDS. The overall reported mortality was defined as either the intensive care unit (ICU) mortality, in-hospital mortality, or mortality within 90 days, and short-term mortality was defined as ICU-mortality, in-hospital mortality, or mortality within 30 days.

Results

We included 9 studies (N = 1861 patients) in this meta-analysis. RV injury that included RV dysfunction, RV dysfunction with hemodynamic compromise, RV failure, or acute cor-pulmonale was present in 21.0% (391/1,861). In the pooled meta-analysis, the presence of RV injury in patients with ARDS was associated with significantly higher overall mortality (OR 1.45, 95% CI 1.13–1.86, p-value = 0.003, I2 = 0%), as well as short-term mortality (OR 1.48, 95% CI 1.14–1.93, p-value = 0.003, I2 = 0%).

Conclusion

In this systematic review and meta-analysis including 1861 patients with ARDS, the presence of RV injury was significantly associated with increased overall and short-term mortality.