Other bulletins in this series include:

Breast Surgery

Thursday, 28 January 2021

Effectiveness of Bundle Interventions on ICU Delirium: A Meta-Analysis*


Effectiveness of Bundle Interventions on ICU Delirium: A Meta-Analysis*


by Zhang, Shan; Han, Yuan; Xiao, Qian; Li, Haibin; Wu, Ying 


Critical Care Medicine: February 2021 - Volume 49 - Issue 2 - p 335-346



To evaluate the impact of bundle interventions on ICU delirium prevalence, duration, and other patients’ adverse outcomes.

Data Sources: 

The Cochrane Library, PubMed, CINAHL, EMBASE, PsychINFO, and MEDLINE from January 2000 to July 2020. The protocol of the study was registered in International prospective register of systematic reviews (CRD42020163147).

Study Selection: 

Randomized clinical trials or cohort studies that examined the following outcomes were included in the current study: ICU delirium prevalence and duration, proportion of patient-days with coma, ventilator-free days, mechanical ventilation days, ICU or hospital length of stay, and ICU or inhospital or 28-day mortality.

Data Extraction: 

Using a standardized data-collection form, two authors screened the studies and extracted the data independently, and assessed the studies’ quality using the Modified Jadad Score Scale for randomized clinical trials and the Newcastle-Ottawa Scale for cohort studies.

Data Synthesis: 

Eleven studies with a total of 26,384 adult participants were included in the meta-analysis. Five studies (three randomized clinical trials and two cohort studies) involving 18,638 patients demonstrated that ICU delirium prevalence was not reduced (risk ratio = 0.92; 95% CI, 0.68–1.24). Meta-analysis showed that the use of bundle interventions was not associated with shortening the duration of ICU delirium (mean difference = –1.42 d; 95% CI, –3.06 to 0.22; two randomized clinical trials and one cohort study), increasing ventilator-free days (mean difference = 1.56 d; 95% CI, –1.56 to 4.68; three randomized clinical trials), decreasing mechanical ventilation days (mean difference = –0.83 d; 95% CI, –1.80 to 0.14; four randomized clinical trials and two cohort studies), ICU length of stay (mean difference = –1.08 d; 95% CI, –2.16 to 0.00; seven randomized clinical trials and two cohort studies), and inhospital mortality (risk ratio = 0.86; 95% CI, 0.70–1.06; five randomized clinical trials and four cohort studies). However, bundle interventions are effective in reducing the proportion of patient-days experiencing coma (risk ratio = 0.47; 95% CI, 0.39–0.57; two cohort studies), hospital length of stay (mean difference = –1.47 d; 95% CI, –2.80 to –0.15; four randomized clinical trials and one cohort study), and 28-day mortality by 18% (risk ratio = 0.82; 95% CI, 0.69–0.99; three randomized clinical trials).


This meta-analysis fails to support that bundle interventions are effective in reducing ICU delirium prevalence and duration, but supports that bundle interventions are effective in reducing the proportion of patient-days with coma, hospital length of stay, and 28-day mortality. Larger randomized clinical trials are needed to evaluate the impact of bundle interventions on ICU delirium and other clinical outcomes.

Is Cardiopulmonary Resuscitation Futile in Coronavirus Disease 2019 Patients Experiencing In-Hospital Cardiac Arrest?*


Is Cardiopulmonary Resuscitation Futile in Coronavirus Disease 2019 Patients Experiencing In-Hospital Cardiac Arrest?*


by Shah, Priyank; Smith, Hallie; Olarewaju, Ayodeji; Jani, Yash; Cobb, Abigail; Owens, Jack; Moore, Justin; Chenna, Avantika; Hess, David 


Critical Care Medicine: February 2021 - Volume 49 - Issue 2 - p 201-208



There is limited data regarding outcomes after in-hospital cardiac arrest among coronavirus disease 2019 patients. None of the studies have reported the outcomes of in-hospital cardiac arrest in coronavirus disease 2019 patients in the United States. We describe the characteristics and outcomes of in-hospital cardiac arrest in coronavirus disease 2019 patients in rural Southwest Georgia.


Retrospective cohort study.


Single-center, multihospital.


Consecutive coronavirus disease 2019 patients who experienced in-hospital cardiac arrest with attempted resuscitation.


Attempted resuscitation with advanced cardiac life support.

Measurement and Main Results: 

Out of 1,094 patients hospitalized for coronavirus disease 2019 during the study period, 63 patients suffered from in-hospital cardiac arrest with attempted resuscitation and were included in this study. The median age was 66 years, and 49.2% were males. The majority of patients were African Americans (90.5%). The most common comorbidities were hypertension (88.9%), obesity (69.8%), diabetes (60.3%), and chronic kidney disease (33.3%). Eighteen patients (28.9%) had a Charlson Comorbidity Index of 0–2. The most common presenting symptoms were shortness of breath (63.5%), fever (52.4%), and cough (46%). The median duration of symptoms prior to admission was 14 days. During hospital course, 66.7% patients developed septic shock, and 84.1% had acute respiratory distress syndrome. Prior to in-hospital cardiac arrest, 81% were on ventilator, 60.3% were on vasopressors, and 39.7% were on dialysis. The majority of in-hospital cardiac arrest (84.1%) occurred in the ICU. Time to initiation of advanced cardiac life support protocol was less than 1 minute for all in-hospital cardiac arrest in the ICU and less than 2 minutes for the remaining patients. The most common initial rhythms were pulseless electrical activity (58.7%) and asystole (33.3%). Although return of spontaneous circulation was achieved in 29% patients, it was brief in all of them. The in-hospital mortality was 100%.


In our study, coronavirus disease 2019 patients suffering from in-hospital cardiac arrest had 100% in-hospital mortality regardless of the baseline comorbidities, presenting illness severity, and location of arrest.


Early Percutaneous Tracheostomy in Coronavirus Disease 2019: Association With Hospital Mortality and Factors Associated With Removal of Tracheostomy Tube at ICU Discharge. A Cohort Study on 121 Patients*


by Rosano, Antonio; Martinelli, Enrico; Fusina, Federica; Albani, Filippo; Caserta, Rosalba; Morandi, Alessandro; Dell’Agnolo, Piera; Dicembrini, Alessandra; Mansouri, Leila; Marchini, Andrea; Schivalocchi, Valeria; Natalini, Giuseppe 

Critical Care Medicine: February 2021 - Volume 49 - Issue 2 - p 261-270


Objectives: Early tracheotomy, defined as a procedure performed within 10 days from intubation, is associated with more ventilator free days, shorter ICU stay, and lower mortality than late tracheotomy. During the coronavirus disease 2019 pandemic, it was especially important to save operating room resources and to have a shorter ICU stay for patients, when ICUs had insufficient beds. In this context of limited resources, early percutaneous tracheostomy could be an effective way to manage mechanically ventilated patients. Nevertheless, current recommendations suggest delaying or avoiding the tracheotomy in coronavirus disease 2019 patients. Aim of the study was to analyze the hospital mortality of coronavirus disease 2019 patients who had received early percutaneous tracheostomy and factors associated with removal of tracheostomy cannula at ICU discharge.

Design: Cohort study. Setting: Coronavirus disease 2019 ICU.

Patients: Adult patients with coronavirus disease 2019 3 days after ICU admission. Interventions: None.

Measurements and Main Results: Three days after ICU admission, 164 patients were present in ICU and included in the analysis. One-hundred and twenty-one patients (74%) were tracheostomized, whereas the other 43 (26%) were managed with translaryngeal intubation only. In multivariable analysis, early percutaneous tracheostomy was associated with lower hospital mortality. Sixty-six of tracheostomized patients (55%) were discharged alive from the hospital. Age and male sex were the only characteristics that were independently associated with mortality in the tracheostomized patients (45.5% and 62.8% in tracheostomized and nontracheostomized patients, respectively; p = 0.009). Tracheostomy tube was removed in 47 of the tracheostomized patients (71%). The only variable independently associated with weaning from tracheostomy at ICU discharge was a faster start of spontaneous breathing after tracheotomy was performed.

Conclusions: Early percutaneous tracheostomy was safe and effective in coronavirus disease 2019 patients, giving a good chance of survival and of weaning from tracheostomy cannula at ICU discharge.





Duration of diaphragmatic inactivity after endotracheal intubation of critically ill patients


Duration of diaphragmatic inactivity after endotracheal intubation of critically ill patients


by Michael Chaim Sklar, Fabiana Madotto, Annemijn Jonkman, Michela Rauseo, Ibrahim Soliman, L. Felipe Damiani, Irene Telias, Sebastian Dubo, Lu Chen, Nuttapol Rittayamai, Guang-Qiang Chen, Ewan C. Goligher, Martin Dres, Remi Coudroy, Tai Pham, Ricard M. Artigas…


Critical Care volume 25, Article number: 26 (2021)



In patients intubated for mechanical ventilation, prolonged diaphragm inactivity could lead to weakness and poor outcome. Time to resume a minimal diaphragm activity may be related to sedation practice and patient severity.


Prospective observational study in critically ill patients. Diaphragm electrical activity (EAdi) was continuously recorded after intubation looking for resumption of a minimal level of diaphragm activity (beginning of the first 24 h period with median EAdi > 7 µV, a threshold based on literature and correlations with diaphragm thickening fraction). Recordings were collected until full spontaneous breathing, extubation, death or 120 h. A 1 h waveform recording was collected daily to identify reverse triggering.


Seventy-five patients were enrolled and 69 analyzed (mean age ± standard deviation 63 ± 16 years). Reasons for ventilation were respiratory (55%), hemodynamic (19%) and neurologic (20%). Eight catheter disconnections occurred. The median time for resumption of EAdi was 22 h (interquartile range 0–50 h); 35/69 (51%) of patients resumed activity within 24 h while 4 had no recovery after 5 days. Late recovery was associated with use of sedative agents, cumulative doses of propofol and fentanyl, controlled ventilation and age (older patients receiving less sedation). Severity of illness, oxygenation, renal and hepatic function, reason for intubation were not associated with EAdi resumption. At least 20% of patients initiated EAdi with reverse triggering.


Low levels of diaphragm electrical activity are common in the early course of mechanical ventilation: 50% of patients do not recover diaphragmatic activity within one day. Sedatives are the main factors accounting for this delay independently from lung or general severity.

Ventilator-associated pneumonia in critically ill patients with COVID-19

 Ventilator-associated pneumonia in critically ill patients with COVID-19


by Mailis Maes, Ellen Higginson, Joana Pereira-Dias, Martin D. Curran, Surendra Parmar, Fahad Khokhar, Delphine Cuchet-Lourenço, Janine Lux, Sapna Sharma-Hajela, Benjamin Ravenhill, Islam Hamed, Laura Heales, Razeen Mahroof, Amelia Solderholm, Sally Forrest, Sushmita Sridhar…


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



Pandemic COVID-19 caused by the coronavirus SARS-CoV-2 has a high incidence of patients with severe acute respiratory syndrome (SARS). Many of these patients require admission to an intensive care unit (ICU) for invasive ventilation and are at significant risk of developing a secondary, ventilator-associated pneumonia (VAP).


To study the incidence of VAP and bacterial lung microbiome composition of ventilated COVID-19 and non-COVID-19 patients.


In this retrospective observational study, we compared the incidence of VAP and secondary infections using a combination of microbial culture and a TaqMan multi-pathogen array. In addition, we determined the lung microbiome composition using 16S RNA analysis in a subset of samples. The study involved 81 COVID-19 and 144 non-COVID-19 patients receiving invasive ventilation in a single University teaching hospital between March 15th 2020 and August 30th 2020.


COVID-19 patients were significantly more likely to develop VAP than patients without COVID (Cox proportional hazard ratio 2.01 95% CI 1.14–3.54, p = 0.0015) with an incidence density of 28/1000 ventilator days versus 13/1000 for patients without COVID (p = 0.009). Although the distribution of organisms causing VAP was similar between the two groups, and the pulmonary microbiome was similar, we identified 3 cases of invasive aspergillosis amongst the patients with COVID-19 but none in the non-COVID-19 cohort. Herpesvirade activation was also numerically more frequent amongst patients with COVID-19.


COVID-19 is associated with an increased risk of VAP, which is not fully explained by the prolonged duration of ventilation. The pulmonary dysbiosis caused by COVID-19, and the causative organisms of secondary pneumonia observed are similar to that seen in critically ill patients ventilated for other reasons.

Knowledge translation tools to guide care of non-intubated patients with acute respiratory illness during the COVID-19 Pandemic


Knowledge translation tools to guide care of non-intubated patients with acute respiratory illness during the COVID-19 Pandemic


by David Leasa, Paul Cameron, Kimia Honarmand, Tina Mele and Karen J. Bosma 


Critical Care volume 25, Article number: 22 (2021) 


Providing optimal care to patients with acute respiratory illness while preventing hospital transmission of COVID-19 is of paramount importance during the pandemic; the challenge lies in achieving both goals simultaneously. Controversy exists regarding the role of early intubation versus use of non-invasive respiratory support measures to avoid intubation. This review summarizes available evidence and provides a clinical decision algorithm with risk mitigation techniques to guide clinicians in care of the hypoxemic, non-intubated, patient during the COVID-19 pandemic. Although aerosolization of droplets may occur with aerosol-generating medical procedures (AGMP), including high flow nasal oxygen and non-invasive ventilation, the risk of using these AGMP is outweighed by the benefit in carefully selected patients, particularly if care is taken to mitigate risk of viral transmission. Non-invasive support measures should not be denied for conditions where previously proven effective and may be used even while there is suspicion of COVID-19 infection. Patients with de novo acute respiratory illness with suspected/confirmed COVID-19 may also benefit. These techniques may improve oxygenation sufficiently to allow some patients to avoid intubation; however, patients must be carefully monitored for signs of increased work of breathing. Patients showing signs of clinical deterioration or high work of breathing not alleviated by non-invasive support should proceed promptly to intubation and invasive lung protective ventilation strategy. With adherence to these principles, risk of viral spread can be minimized.

Management of late onset urea cycle disorders—a remaining challenge for the intensivist?

 Management of late onset urea cycle disorders—a remaining challenge for the intensivist?


by S. Redant, A. Empain, A. Mugisha, P. Kamgang, R. Attou, P. M. Honoré and D. De Bels 


Annals of Intensive Care volume 11, Article number: 2 (2021) 



Hyperammonemia caused by a disorder of the urea cycle is a rare cause of metabolic encephalopathy that may be underdiagnosed by the adult intensivists because of its rarity. Urea cycle disorders are autosomal recessive diseases except for ornithine transcarbamylase deficiency (OTCD) that is X-linked. Optimal treatment is crucial to improve prognosis.

Main body

We systematically reviewed cases reported in the literature on hyperammonemia in adulthood. We used the US National Library of Medicine Pubmed search engine since 2009. The two main causes are ornithine transcarbamylase deficiency followed by type II citrullinemia. Diagnosis by the intensivist remains very challenging therefore delaying treatment and putting patients at risk of fatal cerebral edema. Treatment consists in adapted nutrition, scavenging agents and dialysis. As adults are more susceptible to hyperammonemia, emergent hemodialysis is mandatory before referral to a reference center if ammonia levels are above 200 µmol/l as the risk of cerebral edema is then above 55%. Definitive therapy in urea cycle abnormalities is liver transplantation.


Awareness of urea cycle disorders in adults intensive care units can optimize early management and accordingly dramatically improve prognosis. By preventing hyperammonemia to induce brain edema and herniation leading to death.

Systematic early versus late mobilization or standard early mobilization in mechanically ventilated adult ICU patients: systematic review and meta-analysis

 Systematic early versus late mobilization or standard early mobilization in mechanically ventilated adult ICU patients: systematic review and meta-analysis


by Dominik Menges, Bianca Seiler, Yuki Tomonaga, Matthias Schwenkglenks, Milo A. Puhan and Henock G. Yebyo 


Critical Care volume 25, Article number: 16 (2021)



This systematic review and meta-analysis aimed to determine the effectiveness of systematic early mobilization in improving muscle strength and physical function in mechanically ventilated intensive care unit (ICU) patients.


We conducted a two-stage systematic literature search in MEDLINE, EMBASE and the Cochrane Library until January 2019 for randomized controlled trials (RCTs) examining the effects of early mobilization initiated within 7 days after ICU admission compared with late mobilization, standard early mobilization or no mobilization. Priority outcomes were Medical Research Council Sum Score (MRC-SS), incidence of ICU-acquired weakness (ICUAW), 6-min walk test (6MWT), proportion of patients reaching independence, time needed until walking, SF-36 Physical Function Domain Score (PFS) and SF-36 Physical Health Component Score (PCS). Meta-analysis was conducted where sufficient comparable evidence was available. We evaluated the certainty of evidence according to the GRADE approach.


We identified 12 eligible RCTs contributing data from 1304 participants. Two RCTs were categorized as comparing systematic early with late mobilization, nine with standard early mobilization and one with no mobilization. We found evidence for a benefit of systematic early mobilization compared to late mobilization for SF-36 PFS (MD 12.3; 95% CI 3.9–20.8) and PCS (MD 3.4; 95% CI 0.01–6.8), as well as on the proportion of patients reaching independence and the time needed to walking, but not for incidence of ICUAW (RR 0.62; 95% CI 0.38–1.03) or MRC-SS. For systematic early compared to standard early mobilization, we found no statistically significant benefit on MRC-SS (MD 5.8; 95% CI − 1.4 to 13.0), incidence of ICUAW (RR 0.90; 95% CI 0.63–1.27), SF-36 PFS (MD 8.1; 95% CI − 15.3 to 31.4) or PCS (MD − 2.4; 95% CI − 6.1 to 1.3) or other priority outcomes except for change in 6MWT from baseline. Generally, effects appeared stronger for systematic early compared to late mobilization than to standard early mobilization. We judged the certainty of evidence for all outcomes as very low to low.


The evidence regarding a benefit of systematic early mobilization remained inconclusive. However, our findings indicate that the larger the difference in the timing between the intervention and the comparator, the more likely an RCT is to find a benefit for early mobilization.

Critical Care Management of the Patient with Clostridioides difficile


Critical Care Management of the Patient with Clostridioides difficile


by Adelman, Max W.; Woodworth, Michael H.; Shaffer, Virginia O.; Martin, Greg S.; Kraft, Colleen S. 


Critical Care Medicine: January 2021 - Volume 49 - Issue 1 - p 127-139



To review published clinical evidence on management of Clostridioides difficile infection in critically ill patients.

DATA SOURCES: We obtained relevant studies from a PubMed literature review and bibliographies of reviewed articles.

STUDY SELECTION: We selected English-language studies addressing aspects of C. difficile infection relevant to critical care clinicians including epidemiology, risk factors, diagnosis, treatment, and prevention, with a focus on high-quality clinical evidence.

DATA EXTRACTION: We reviewed potentially relevant studies and abstracted information on study design, methods, patient selection, and results of relevant studies. This is a synthetic (i.e., not systematic) review.

DATA SYNTHESIS: C. difficile infection is the most common healthcare-associated infection in the United States. Antibiotics are the most significant C. difficile infection risk factor, and among antibiotics, cephalosporins, clindamycin, carbapenems, fluoroquinolones, and piperacillin-tazobactam confer the highest risk. Age, diabetes mellitus, inflammatory bowel disease, and end-stage renal disease are risk factors for C. difficile infection development and mortality. C. difficile infection diagnosis is based on testing appropriately selected patients with diarrhea or on clinical suspicion for patients with ileus. Patients with fulminant disease (C. difficile infection with hypotension, shock, ileus, or megacolon) should be treated with oral vancomycin and IV metronidazole, as well as rectal vancomycin in case of ileus. Patients who do not respond to initial therapy should be considered for fecal microbiota transplant or surgery. Proper infection prevention practices decrease C. difficile infection risk.

CONCLUSIONS: Strong clinical evidence supports limiting antibiotics when possible to decrease C. difficile infection risk. For patients with fulminant C. difficile infection, oral vancomycin reduces mortality, and adjunctive therapies (including IV metronidazole) and interventions (including fecal microbiota transplant) may benefit select patients. Several important questions remain regarding fulminant C. difficile infection management, including which patients benefit from fecal microbiota transplant or surgery.

Clinical application of esophageal manometry: how I do it


Clinical application of esophageal manometry: how I do it


by Elias Baedorf Kassis and Daniel Talmor 


Critical Care volume 25, Article number: 6 (2021) 


Our group uses esophageal manometry routinely to personalize mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) [12]. Esophageal pressures (Pes) allow for differentiation of chest wall, lung and respiratory system mechanics, and we use this for PEEP titration [12], monitoring of parenchymal lung stress, limiting peak end-inspiratory transpulmonary pressures and monitoring for ventilator synchrony [34].

We find that esophageal manometry is straightforward in the majority of patients although proper training and application are important. The initial step is to assure correct placement with insertion of stand-alone catheters or feeding tubes with integrated esophageal balloons which are similar to routine gastric tubes. Typical depth of insertion ranges from 33 to 40 cm, depending on body size and we assure proper placement through functional bedside assessment. First, we look for the presence of cardiac oscillations to assure correct position posterior to the heart. If absent, this suggests the balloon is too deep or shallow and we incrementally adjust while monitoring for these oscillations. Next we perform expiratory breath holds, with changes in Pes, airway (Pao) and transpulmonary pressure (PL = Pao − Pes) monitored during gentle chest pushes. Proper position is confirmed when Pes and Pao increase in equal measure, with no change in the calculated PL. If Pao increases more Pes, this suggests that position is too deep and the balloon is adjusted incrementally with repeat chest pushes. This may be confirmed with gentle abdominal pushes (with Pes increasing more than Pao). (Table 1)…

Accelerated versus standard initiation of renal replacement therapy for critically ill patients with acute kidney injury: a systematic review and meta-analysis of RCT studies


Accelerated versus standard initiation of renal replacement therapy for critically ill patients with acute kidney injury: a systematic review and meta-analysis of RCT studies


by Heng-Chih Pan, Ying-Ying Chen, I-Jung Tsai, Chih-Chung Shiao, Tao-Min Huang, Chieh-Kai Chan, Hung-Wei Liao, Tai-Shuan Lai, Yvonne Chueh, Vin-Cent Wu and Yung-Ming Chen 


Critical Care volume 25, Article number: 5 (2021)



Acute kidney injury (AKI) is a common yet possibly fatal complication among critically ill patients in intensive care units (ICU). Although renal replacement therapy (RRT) is an important supportive management for severe AKI patients, the optimal timing of RRT initiation for these patients is still unclear.


In this systematic review, we searched all relevant randomized controlled trials (RCTs) that directly compared accelerated with standard initiation of RRT from PUBMED, MEDLINE, EMBASE, and Cnki.net published prior to July, 20, 2020. We extracted study characteristics and outcomes of being free of dialysis, dialysis dependence and mortality. We rated the certainty of evidence according to Cochrane methods and the GRADE approach.


We identified 56 published relevant studies from 1071 screened abstracts. Ten RCTs with 4753 critically ill AKI patients in intensive care unit (ICU) were included in this meta-analysis. In our study, accelerated and standard RRT group were not associated with all-cause mortality (log odds-ratio [OR]: − 0.04, 95% confidence intervals [CI] − 0.16 to 0.07, p = 0.46) and free of dialysis (log OR: − 0.03, 95% CI − 0.14 to 0.09, p = 0.65). In the subgroup analyses, accelerated RRT group was significantly associated with lower risk of all-cause mortality in the surgical ICU and for those who received continuous renal replacement therapy (CRRT). In addition, patients in these two subgroups had higher chances of being eventually dialysis-free. However, accelerated initiation of RRT augmented the risk of dialysis dependence in the subgroups of patients treated with non-CRRT modality and whose Sequential Organ Failure Assessment (SOFA) score were more than 11.


In this meta-analysis, critically ill patients with severe AKI would benefit from accelerated RRT initiation regarding all-cause mortality and being eventually free of dialysis only if they were surgical ICU patients or if they underwent CRRT treatment. However, the risk of dialysis dependence was increased in the accelerated RRT group when those patients used non-CRRT modality or had high SOFA scores. All the literatures reviewed in this study were highly heterogeneous and potentially subject to biases.

Comparison between first and second wave among critically ill COVID-19 patients admitted to a French ICU: no prognostic improvement during the second wave?


Comparison between first and second wave among critically ill COVID-19 patients admitted to a French ICU: no prognostic improvement during the second wave?


by Damien Contou, Megan Fraissé, Olivier Pajot, Jo-Anna Tirolien, Hervé Mentec and Gaëtan Plantefève 


Critical Care volume 25, Article number: 3 (2021)


As many countries in Europe, France faced a second wave COVID-19 pandemic since September, 2020. During the first wave, intensivists faced an unprecedented massive admission of patients with COVID-19 pneumonia requiring invasive mechanical ventilation, sometimes leading to ICUs saturation. They discovered the stereotypical course of this previously unknown disease with its own specificities including the need for deep sedation and neuromuscular blockade, the increased risk of thrombotic and hemorrhagic events [12], and the prolonged duration of mechanical ventilation [3] with high rate of delirium [4]. Importantly, several randomized controlled trials conducted during this first wave highlighted the beneficial effects of early administration of glucocorticoids for critically ill COVID-19 patients [56].

One can legitimately assume that the experience gained during the first wave may have contributed to a better management and outcome among critically ill COVID-19 patients admitted during the second wave.

We therefore compared the characteristics and the outcome between patients admitted to our 41-bed COVID-19 ICU for acute respiratory failure due to COVID-19 (RT-PCR positive for SARS-CoV-2) during the first wave (from March 13th to May 27th, 2020) and those admitted to our 18-bed ICU during the second wave (from August 19th to December 7th, 2020).

COVID-19 patients without acute respiratory failure, those transferred to other ICUs or still hospitalized in ICU were not included.

Early corticosteroids are associated with lower mortality in critically ill patients with COVID-19: a cohort study


Early corticosteroids are associated with lower mortality in critically ill patients with COVID-19: a cohort study


by Pablo Monedero, Alfredo Gea, Pedro Castro, Angel M. Candela-Toha, María L. Hernández-Sanz, Egoitz Arruti, Jesús Villar and Carlos Ferrando 


Critical Care volume 25, Article number: 2 (2021)



Critically ill patients with coronavirus disease 19 (COVID-19) have a high fatality rate likely due to a dysregulated immune response. Corticosteroids could attenuate this inappropriate response, although there are still some concerns regarding its use, timing, and dose.


This is a nationwide, prospective, multicenter, observational, cohort study in critically ill adult patients with COVID-19 admitted into Intensive Care Units (ICU) in Spain from 12th March to 29th June 2020. Using a multivariable Cox model with inverse probability weighting, we compared relevant outcomes between patients treated with early corticosteroids (before or within the first 48 h of ICU admission) with those who did not receive early corticosteroids (delayed group) or any corticosteroids at all (never group). Primary endpoint was ICU mortality. Secondary endpoints included 7-day mortality, ventilator-free days, and complications.


A total of 691 patients out of 882 (78.3%) received corticosteroid during their hospital stay. Patients treated with early-corticosteroids (n = 485) had lower ICU mortality (30.3% vs. never 36.6% and delayed 44.2%) and lower 7-day mortality (7.2% vs. never 15.2%) compared to non-early treated patients. They also had higher number of ventilator-free days, less length of ICU stay, and less secondary infections than delayed treated patients. There were no differences in medical complications between groups. Of note, early use of moderate-to-high doses was associated with better outcomes than low dose regimens.


Early use of corticosteroids in critically ill patients with COVID-19 is associated with lower mortality than no or delayed use, and fewer complications than delayed use.

Tuesday, 29 December 2020

Risks of ventilator-associated pneumonia and invasive pulmonary aspergillosis in patients with viral acute respiratory distress syndrome related or not to Coronavirus 19 disease


Risks of ventilator-associated pneumonia and invasive pulmonary aspergillosis in patients with viral acute respiratory distress syndrome related or not to Coronavirus 19 disease


by Keyvan Razazi, Romain Arrestier, Anne Fleur Haudebourg, Brice Benelli, Guillaume Carteaux, Jean‑Winoc Decousser, Slim Fourati, Paul Louis Woerther, Frederic Schlemmer, Anais Charles-Nelson, Francoise Botterel, Nicolas de Prost and Armand Mekontso Dessap


Critical Care volume 24, Article number: 699 (2020) Published: 18 December 2020



Data on incidence of ventilator-associated pneumonia (VAP) and invasive pulmonary aspergillosis in patients with severe SARS-CoV-2 infection are limited.


We conducted a monocenter retrospective study comparing the incidence of VAP and invasive aspergillosis between patients with COVID-19-related acute respiratory distress syndrome (C-ARDS) and those with non-SARS-CoV-2 viral ARDS (NC-ARDS).


We assessed 90 C-ARDS and 82 NC-ARDS patients, who were mechanically ventilated for more than 48 h. At ICU admission, there were significantly fewer bacterial coinfections documented in C-ARDS than in NC-ARDS: 14 (16%) vs 38 (48%), p < 0.01. Conversely, significantly more patients developed at least one VAP episode in C-ARDS as compared with NC-ARDS: 58 (64%) vs. 36 (44%), p = 0.007. The probability of VAP was significantly higher in C-ARDS after adjusting on death and ventilator weaning [sub-hazard ratio = 1.72 (1.14–2.52), p < 0.01]. The incidence of multi-drug-resistant bacteria (MDR)-related VAP was significantly higher in C-ARDS than in NC-ARDS: 21 (23%) vs. 9 (11%), p = 0.03. Carbapenem was more used in C-ARDS than in NC-ARDS: 48 (53%), vs 21 (26%), p < 0.01. According to AspICU algorithm, there were fewer cases of putative aspergillosis in C-ARDS than in NC-ARDS [2 (2%) vs. 12 (15%), p = 0.003], but there was no difference in Aspergillus colonization.


In our experience, we evidenced a higher incidence of VAP and MDR-VAP in C-ARDS than in NC-ARDS and a lower risk for invasive aspergillosis in the former group.

Resuscitation fluid types in sepsis, surgical, and trauma patients: a systematic review and sequential network meta-analyses


Resuscitation fluid types in sepsis, surgical, and trauma patients: a systematic review and sequential network meta-analyses


by Chien-Hua Tseng, Tzu-Tao Chen, Mei-Yi Wu, Ming-Cheng Chan, Ming-Chieh Shih and Yu-Kang Tu 

Critical Care volume 24, Article number: 693 (2020) Published: 14 December 2020


Crystalloids and different component colloids, used for volume resuscitation, are sometimes associated with various adverse effects. Clinical trial findings for such fluid types in different patients’ conditions are conflicting. Whether the mortality benefit of balanced crystalloid than saline can be inferred from sepsis to other patient group is uncertain, and adverse effect profile is not comprehensive. This study aims to compare the survival benefits and adverse effects of seven fluid types with network meta-analysis in sepsis, surgical, trauma, and traumatic brain injury patients.


Searched databases (PubMed, EMBASE, and Cochrane CENTRAL) and reference lists of relevant articles occurred from inception until January 2020. Studies on critically ill adults requiring fluid resuscitation were included. Intervention studies reported on balanced crystalloid, saline, iso-oncotic albumin, hyperoncotic albumin, low molecular weight hydroxyethyl starch (L-HES), high molecular weight HES, and gelatin. Network meta-analyses were conducted using random-effects model to calculate odds ratio (OR) and mean difference. Risk of Bias tool 2.0 was used to assess bias. Confidence in Network Meta-Analysis (CINeMA) web application was used to rate confidence in synthetic evidence.


Fifty-eight trials (n = 26,351 patients) were identified. Seven fluid types were evaluated. Among patients with sepsis and surgery, balanced crystalloids and albumin achieved better survival, fewer acute kidney injury, and smaller blood transfusion volumes than saline and L-HES. In those with sepsis, balanced crystalloids significantly reduced mortality more than saline (OR 0.84; 95% CI 0.74–0.95) and L-HES (OR 0.81; 95% CI 0.69–0.95) and reduced acute kidney injury more than L-HES (OR 0.80; 95% CI 0.65–0.99). However, they required the greatest resuscitation volume among all fluid types, especially in trauma patients. In patients with traumatic brain injury, saline and L-HES achieved lower mortality than albumin and balanced crystalloids; especially saline was significantly superior to iso-oncotic albumin (OR 0.55; 95% CI 0.35–0.87).


Our network meta-analysis found that balanced crystalloids and albumin decreased mortality more than L-HES and saline in sepsis patients; however, saline or L-HES was better than iso-oncotic albumin or balanced crystalloids in traumatic brain injury patients.