Other bulletins in this series include:

Breast Surgery

Tuesday, 19 May 2020

Letter: Advanced respiratory monitoring in COVID-19 patients: use less PEEP!

by Lisanne Roesthuis, Maarten van den Berg and Hans van der Hoeven

Critical Care volume 24, Article number: 230 (2020) Published: 15 May 2020

In the majority of coronavirus disease 2019 (COVID-19) patients, respiratory mechanics is different from the “normal” acute respiratory distress syndrome (ARDS) patient. Plateau pressures and driving pressures are often low and respiratory system compliance relatively normal compared to the ARDS patient [1]. Many physicians use high positive end-expiratory pressure (PEEP) for patients with COVID-19 although the potential for recruitment is often low [12]. We fear that the high compliance of the respiratory system in combination with high PEEP will lead to hyperinflation, high dead space, and potentially right ventricular failure.

We have used the following strategy for COVID-19 patients (N = 70): after intubation, immediately prone positioning for at least 3 days, using the lowest possible PEEP to obtain adequate oxygenation with FiO2 of 50%. We assessed the effects of different PEEP levels on respiratory mechanics and ventilation-perfusion mismatching.

Prolonged prone position ventilation for SARS-CoV-2 patients is feasible and effective

by Andrea Carsetti, Agnese Damia Paciarini, Benedetto Marini, Simona Pantanetti, Erica Adrario and Abele Donati

Critical Care volume 24, Article number: 225 (2020) Published: 15 May 2020

Recently, novel coronavirus 2019 (nCOV-19) is spreading all around the world causing severe acute respiratory syndrome (SARS-CoV-2) requiring mechanical ventilation in about 5% of infected people [12]. Prone position ventilation is an established method to improve oxygenation in severe acute respiratory distress syndrome (ARDS), and its application was able to reduce mortality rate [3]. Although the severity of critically ill patients with SARS-CoV-2 may require pronation [4], the huge number of patients requiring intensive care unit (ICU) admission may create management problems due to the limited number of healthcare workers compared to the number of patients. Often, sustained oxygenation improvement can only be achieved after several cycles of pronation, with a work overload for healthcare staff. To face these problems, we implemented a pronation protocol that allows to extend the time for the prone position beyond 16 h, aiming to reduce the number of pronation cycles per patient. Thus, the aim of this report was to assess the feasibility and efficacy of prone position ventilation beyond the usual 16 h...

Our recommendations for acute management of COVID-19

by Francesco Mojoli, Silvia Mongodi, Anita Orlando, Eric Arisi, Marco Pozzi, Luca Civardi, Guido Tavazzi, Fausto Baldanti, Raffaele Bruno and Giorgio Antonio Iotti

Critical Care volume 24, Article number: 207 (2020) Published: 08 May 2020

The 2019 coronavirus disease (COVID-19) epidemic is currently spreading worldwide; in particular, Italy and our region (Lombardy) have been facing the largest European outbreak since February 21st [1]. We here share our practical clinical management suggestions, derived from the direct experience of the first 200 patients with acute respiratory failure, of which 75 were finally admitted to intensive care unit (ICU) to undergo mechanical ventilation…

Furosemide stress test as a predictive marker of acute kidney injury progression or renal replacement therapy: a systemic review and meta-analysis

by Jia-Jin Chen, Chih-Hsiang Chang, Yen-Ta Huang and George Kuo

Critical Care volume 24, Article number: 202 (2020) Published: 07 May 2020

The use of the furosemide stress test (FST) as an acute kidney injury (AKI) severity marker has been described in several trials. However, the diagnostic performance of the FST in predicting AKI progression has not yet been fully discussed.
In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed, Embase, and Cochrane databases up to March 2020. The diagnostic performance of the FST (in terms of sensitivity, specificity, number of events, true positive, false positive) was extracted and evaluated.
We identified eleven trials that enrolled a total of 1366 patients, including 517 patients and 1017 patients for whom the outcomes in terms of AKI stage progression and renal replacement therapy (RRT), respectively, were reported. The pooled sensitivity and specificity results of the FST for AKI progression prediction were 0.81 (95% CI 0.74–0.87) and 0.88 (95% CI 0.82–0.92), respectively. The pooled positive likelihood ratio (LR) was 5.45 (95% CI 3.96–7.50), the pooled negative LR was 0.26 (95% CI 0.19–0.36), and the pooled diagnostic odds ratio (DOR) was 29.69 (95% CI 17.00–51.85). The summary receiver operating characteristics (SROC) with pooled diagnostic accuracy was 0.88. The diagnostic performance of the FST in predicting AKI progression was not affected by different AKI criteria or underlying chronic kidney disease. The pooled sensitivity and specificity results of the FST for RRT prediction were 0.84 (95% CI 0.72–0.91) and 0.77 (95% CI 0.64–0.87), respectively. The pooled positive LR and pooled negative LR were 3.16 (95% CI 2.06–4.86) and 0.25 (95% CI 0.14–0.44), respectively. The pooled diagnostic odds ratio (DOR) was 13.59 (95% CI 5.74–32.17), and SROC with pooled diagnostic accuracy was 0.86. The diagnostic performance of FST for RRT prediction is better in stage 1–2 AKI compared to stage 3 AKI (relative DOR 5.75, 95% CI 2.51–13.33).
The FST is a simple tool for the identification of AKI populations at high risk of AKI progression and the need for RRT, and the diagnostic performance of FST in RRT prediction is better in early AKI population.

Mean Airway Pressure As a Predictor of 90-Day Mortality in Mechanically Ventilated Patients*

by Sahetya, Sarina K.; Wu, T. David; Morgan, Brooks; Herrera, Phabiola; Roldan, Rollin; Paz, Enrique; Jaymez, Amador A.; Chirinos, Eduardo; Portugal, Jose; Quispe, Rocio; Brower, Roy G.; Checkley, William; Capanni, Francesca; Caravedo, Maria A.; Cerna, Jorge; Davalos, Long; De Ferrari, Aldo; Denney, Joshua A.; Dulanto, Augusto; Mongilardi, Nicole; Paredes, Carmen; Pereda, Maria Alejandra; Shams, Navid; INTENSIVOS Cohort StudyThe INTENSIVOS Cohort Study are as follows

Objectives: To determine the association between mean airway pressure and 90-day mortality in patients with acute respiratory failure requiring mechanical ventilation and to compare the predictive ability of mean airway pressure compared with inspiratory plateau pressure and driving pressure.
Design: Prospective observational cohort.
Setting: Five ICUs in Lima, Peru. Subjects: Adults requiring invasive mechanical ventilation via endotracheal tube for acute respiratory failure. Interventions: None.
Measurements and Main Results: Of potentially eligible participants (n = 1,500), 65 (4%) were missing baseline mean airway pressure, while 352 (23.5%) were missing baseline plateau pressure and driving pressure. Ultimately, 1,429 participants were included in the analysis with an average age of 59 ± 19 years, 45% female, and a mean Pao2/Fio2 ratio of 248 ± 147 mm Hg at baseline. Overall, 90-day mortality was 50.4%. Median baseline mean airway pressure was 13 cm H2O (interquartile range, 10–16 cm H2O) in participants who died compared to a median mean airway pressure of 12 cm H2O (interquartile range, 10–14 cm H2O) in participants who survived greater than 90 days (p < 0.001). Mean airway pressure was independently associated with 90-day mortality (odds ratio, 1.38 for difference comparing the 75th to the 25th percentile for mean airway pressure; 95% CI, 1.10–1.74) after adjusting for age, sex, baseline Acute Physiology and Chronic Health Evaluation III, baseline Pao2/Fio2 (modeled with restricted cubic spline), baseline positive end-expiratory pressure, baseline tidal volume, and hospital site. In predicting 90-day mortality, baseline mean airway pressure demonstrated similar discriminative ability (adjusted area under the curve = 0.69) and calibration characteristics as baseline plateau pressure and driving pressure.
Conclusions: In a multicenter prospective cohort, baseline mean airway pressure was independently associated with 90-day mortality in mechanically ventilated participants and predicts mortality similarly to plateau pressure and driving pressure. Because mean airway pressure is readily available on all mechanically ventilated patients and all ventilator modes, it is a potentially more useful predictor of mortality in acute respiratory failure.

Letter: Liver injury in critically ill patients with COVID-19: a case series

by Filipe S. Cardoso, Rui Pereira and Nuno Germano 

Critical Care volume 24, Article number: 190 (2020) Published: 05 May 2020

Almost all reports on liver injury in patients with 2019 coronavirus disease (COVID-19) found blood liver tests to be frequently abnormal, especially in patients with more severe disease, but with substantial heterogeneity [1]. Moreover, blood liver tests’ abnormalities were frequently thought to be of doubtful clinical value.

Most studies have described blood liver tests in a single time point, usually at inclusion [23]. Therefore, we used our case series of the first 20 consecutive patients with COVID-19 admitted to the intensive care unit (ICU) at Curry Cabral Hospital in Lisbon, Portugal, from March 10, 2020, onwards, to describe the temporal evolution of blood liver tests.

Soluble urokinase plasminogen activator receptor (suPAR) as an early predictor of severe respiratory failure in patients with COVID-19 pneumonia

by Nikoletta Rovina, Karolina Akinosoglou, Jesper Eugen-Olsen, Salim Hayek, Jochen Reiser and Evangelos J. Giamarellos-Bourboulis

Critical Care volume 24, Article number: 187 (2020) Published: 30 April 2020

As of April 1, 2020, 885,689 cases of infections by the novel coronavirus SARS-CoV-2 (COVID-19) have been recorded worldwide; 44,217 of them have died (https://www.worldometers.info/coronavirus). At the beginning of the illness, patients may experience low-degree fever or flu-like symptoms, but suddenly, severe respiratory failure (SRF) emerges [1]. Increased circulating levels of D-dimers [12] suggest endothelial activation. Urokinase plasminogen activator receptor (uPAR) that is bound on the endothelium may be cleaved early during the disease course leading to an increase of its soluble counterpart, namely suPAR [3]. If this holds true, then suPAR may be used as an early predictor of the risk of SRF…

Association between metformin use prior to admission and lower mortality in septic adult patients with diabetes mellitus: beware of potential confounders

by Patrick M. Honore, Aude Mugisha, Luc Kugener, Sebastien Redant, Rachid Attou, Andrea Gallerani and David De Bels

Critical Care volume 24, Article number: 183 (2020) Published: 28 April 2020

We read with great interest the recent paper by Liang et al. who conclude that their meta-analysis indicated an association between metformin (MET) use prior to admission and lower mortality in septic adult patients with diabetes mellitus [1]. We would like to make some comments. Nearly half of critically ill patients, especially those with septic shock, have or develop acute kidney injury (AKI), and 20–25% need renal replacement therapy (RRT) within the first week of their admission [2]. Because of its low molecular weight and minimal protein binding, metformin is equally (highly) eliminated by ultrafiltration (convection) and dialysis (diffusion). Furthermore, its large volume of distribution within a two-compartment pharmacokinetic model implies that metformin may be more effectively cleared by prolonged RRT. This was corroborated by Keller et al., who showed a dramatic reduction of metabolic acidosis and metformin plasma concentrations within the first 24 h after initiating CRRT in patients with MET-induced lactic acidosis, followed by normalization on the second day in all subjects [3]. Although we do not know the exact rate of CRRT in both arms [1], it may well be that one group had more CRRT than the other, particularly the metformin group. For instance, in the study of Doenyas-Barak et al., which had a huge impact on the conclusions of this meta-analysis, the use of RRT was higher in the MET-treated population (38.6 vs. 21.2%, p = 0.13) [14]. Accordingly, we suspect that the observed difference in mortality rate may be due to the more frequent use of RRT in the MET-treated population. A protective effect of RRT has already been suggested by Peters et al., who found that despite higher illness severity, the mortality rate in patients with MET-associated lactic acidosis treated with intermittent hemodialysis (IHD) was no different to that of non-dialyzed subjects [5].

Shining a light on the evidence for hydroxychloroquine in SARS-CoV-2

by Nicholas E. Ingraham, David Boulware, Matthew A. Sparks, Timothy Schacker, Bradley Benson, Jeffrey A. Sparks, Thomas Murray, John Connett, Jeffrey G. Chipman, Anthony Charles and Christopher J. Tignanelli

Critical Care volume 24, Article number: 182 (2020) Published: 28 April 2020

The 2020 COVID-19 pandemic has stunned the world, financial markets, and healthcare systems. Researchers are rushing to identify effective treatments while maintaining rigorous adherence to the scientific method. Clinicians are doing their best to provide evidence-based care in a setting of very little good evidence. To date, no effective treatments exist for COVID-19 management. Unfortunately, traditional and social media coupled with world leader commentary have led some to believe hydroxychloroquine offers a bona fide cure and even prevention. The purpose of this commentary is to review the medical literature related to hydroxychloroquine building on knowledge over the past 17 years since the 2003 SARS-CoV epidemic.

Effect of Antibiotic Discontinuation Strategies on Mortality and Infectious Complications in Critically Ill Septic Patients: A Meta-Analysis and Trial Sequential Analysis*

by Arulkumaran, Nishkantha; Khpal, Muska; Tam, Karen; Baheerathan, Aravindhan; Corredor, Carlos; Singer, Mervyn

Objective: To investigate methods of antibiotic duration minimization and their effect on mortality and infectious complications in critically ill patients.
Data Sources: A systematic search of PubMed, Embase (via Ovid), clinicaltrials.gov, and the Cochrane Central Register of Controlled Trials (via Wiley) (CENTRAL, Issue 2, 2015).
Study Selection: Randomized clinical trials comparing strategies to minimize antibiotic duration (days) for patients with infections or sepsis in intensive care.
Data Extraction: A systematic review with meta-analyses and trial sequential analyses of randomized clinical trials. Dichotomous data are presented as relative risk (95% CIs) and p value, and continuous data are presented as mean difference (CI) and p value.
Data Synthesis: We included 22 randomized clinical trials (6,046 patients). Strategies to minimize antibiotic use included procalcitonin (14 randomized clinical trials), clinical algorithms (two randomized clinical trials), and fixed-antibiotic duration (six randomized clinical trials). Procalcitonin (–1.23 [–1.61 to –0.85]; p < 0.001), but not clinical algorithm–guided antibiotic therapy (–7.41 [–18.18 to 3.37]; p = 0.18), was associated with shorter duration of antibiotic therapy. The intended reduction in antibiotic duration ranged from 3 to 7 days in fixed-duration antibiotic therapy randomized clinical trials. Neither procalcitonin-guided antibiotic treatment (0.91 [0.82–1.01]; p = 0.09), clinical algorithm–guided antibiotic treatment (0.67 [0.30–1.54]; p = 0.35), nor fixed-duration antibiotics (1.21 [0.90–1.63]; p = 0.20) were associated with reduction in mortality. Z-curve for trial sequential analyses of mortality associated with procalcitonin-guided therapy did not reach the trial sequential monitoring boundaries for benefit, harm, or futility (adjusted CI, 0.72–1.10). Trial sequential analyses for mortality associated with clinical algorithm and fixed-duration treatment accumulated less than 5% of the required information size. Despite shorter antibiotic duration, neither procalcitonin-guided therapy (0.93 [0.84–1.03]; p = 0.15) nor fixed-duration antibiotic therapy (1.06 [0.74–1.53]; p = 0.75) was associated with treatment failure.
Conclusions: Although the duration of antibiotic therapy is reduced with procalcitonin-guided therapy or prespecified limited duration, meta-analysis and trial sequential analyses are inconclusive for mortality benefit. Data on clinical algorithms to guide antibiotic cessation are limited.

Biomarkers in the ICU: less is more? Yes

In 1900, Dr. Camac wrote in the Journal of the American Medical Association “Rarely in our science is that any one finding is the open sesame to the secrets of the disease” [1]. In 2020, these words remain relevant, as a reminder that the complexities of both pathophysiology and patient care have always rendered any one test only a part of the puzzle. Regarding biomarkers, definitions vary, with most broad and encompassing many test types [2]. We focus on laboratory-based biomarkers, and contend that before widespread adoption of a given biomarker, we should ask four questions—what is the pretest probability for the diagnosis we are considering, are factors present that interfere with interpretation of the result, will I change management based on the result, and what will the outcome benefit be (Table 1)? We further contend that for many biomarkers, robust answers to these questions are lacking and support this position with illustrative examples of novel and commonly used biomarkers in the ICU.

Facing COVID-19 in the ICU: vascular dysfunction, thrombosis, and dysregulated inflammation

 Current management guidelines for COVID-19 reflect the assumption that critically ill patients infected with SARS-CoV-2 develop acute respiratory distress syndrome (ARDS). However, emerging data and clinical reports increasingly suggest an alternative view that severe COVID-19 reflects a confluence of vascular dysfunction, thrombosis, and dysregulated inflammation…

ICU beds: less is more? Yes

In these extraordinary times, when intensive care unit (ICU) capacity is being outpaced by the dangers of the COVID-19 pandemic, ICU beds are a precious resource. However, when this crisis subsides, we may be left with greatly expanded ICU capacity. We, as intensivists, must act as leaders for our health care systems as there will be an opportunity to reevaluate two core tenets of critical care: (1) the definition of an ICU bed, and (2) the ideal number of ICU beds…

SARS-CoV-2 viral load in sputum correlates with risk of COVID-19 progression

by Xia Yu, Shanshan Sun, Yu Shi, Hao Wang, Ruihong Zhao and Jifang Sheng / 25d//keep unread//hide

Critical Care volume 24, Article number: 170 (2020) Published: 23 April 2020

The pandemic of coronavirus diseases 2019 (COVID-19) imposes a heavy burden on medical resources [1]. Whether there is correlation between viral load and disease severity has not been clarified. In the study, we retrospectively collected the virological data, as well as demographic, epidemiological clinical information of 92 patients with confirmed COVID-19 in a single hospital in Zhejiang Province, China. We compared the baseline viral loads between severe patients and those mild to moderate at admission and also between those developing severe disease during hospitalization and those not…

Platelets and extra-corporeal membrane oxygenation in adult patients: a systematic review and meta-analysis

Despite increasing improvement in extracorporeal membrane oxygenation (ECMO) technology and knowledge, thrombocytopenia and impaired platelet function are usual findings in ECMO patients and the underlying mechanisms are only partially elucidated. The purpose of this meta-analysis and systematic review was to thoroughly summarize and discuss the existing knowledge of platelet profile in adult ECMO population. All studies meeting the inclusion criteria (detailed data about platelet count and function) were selected, after screening literature from July 1975 to August 2019. Twenty-one studies from 1.742 abstracts were selected. The pooled prevalence of thrombocytopenia in ECMO patients was 21% (95% CI 12.9–29.0; 14 studies). Thrombocytopenia prevalence was 25.4% (95% CI 10.6–61.4; 4 studies) in veno-venous ECMO, whereas it was 23.2% (95% CI 11.8–34.5; 6 studies) in veno-arterial ECMO. Heparin-induced thrombocytopenia prevalence was 3.7% (95% CI 1.8–5.5; 12 studies). Meta-regression revealed no significant association between ECMO duration and thrombocytopenia. Platelet function impairment was described in 7 studies. Impaired aggregation was shown in 5 studies, whereas loss of platelet receptors was found in one trial, and platelet activation was described in 2 studies. Platelet transfusions were needed in up to 50% of the patients. Red blood cell transfusions were administered from 46 to 100% of the ECMO patients. Bleeding events varied from 16.6 to 50.7%, although the cause and type of haemorrhage was not consistently reported. Thrombocytopenia and platelet dysfunction are common in ECMO patients, regardless the type of ECMO mode. The underlying mechanisms are multifactorial, and understanding and management are still limited. Further research to design appropriate strategies and protocols for its monitoring, management, or prevention should be matter of thorough investigations.

*Take home message*

Platelet count and function seem to be severely impaired in extracorporeal membrane oxygenation (ECMO) patients. Thrombocytopenia and platelet dysfunction are common in extracorporeal membrane oxygenation (ECMO) patients, regardless the type of ECMO mode.

Therapeutic strategies for critically ill patients with COVID-19

by Lei Li, Ranran Li, Zhixiong Wu, Xianghong Yang, Mingyan Zhao, Jiao Liu and Dechang Chen 

Annals of Intensive Care volume 10, Article number: 45 (2020)

Since the 2019 novel coronavirus disease (COVID-19) outbreak originated from Wuhan, Hubei Province, China, at the end of 2019, it has become a clinical threat to the general population worldwide. Among people infected with the novel coronavirus (2019-nCoV), the intensive management of the critically ill patients in intensive care unit (ICU) needs substantial medical resource. In the present article, we have summarized the promising drugs, adjunctive agents, respiratory supportive strategies, as well as circulation management, multiple organ function monitoring and appropriate nutritional strategies for the treatment of COVID-19 in the ICU based on the previous experience of treating other viral infections and influenza. These treatments are referable before the vaccine and specific drugs are available for COVID-19.

Letter: Critically ill SARS-CoV-2-infected patients are not stratified as sepsis by the qSOFA

by Marion Ferreira, Timothee Blin, Nived Collercandy, Piotr Szychowiak, Pierre-François Dequin, Youenn Jouan and Antoine Guillon

Annals of Intensive Care , volume 10, Article number: 43 (2020) 

The SEPSIS-3 definitions had facilitated earlier recognition of patients at risk of developing sepsis for timely management [1]. The quickSOFA (qSOFA) has emerged as a bedside clinical score to clinically categorize a septic patient. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection are likely to have poor outcomes typical of sepsis if they have at least 2 of the qSOFA criteria: respiratory rate ≥ 22/min, altered mentation, or systolic blood pressure ≤ 100 mmHg [1]. This definition has been subsequently validated in the emergency department for patients with suspected infection: for qSOFA ≤ 1 the mortality rate was 3% (95% CI 2–5%) vs 24% (95% CI 18–30%) for patients with a qSOFA ≥ 2 [2]. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes coronavirus disease 2019 (Covid-19) is a game changer. Mass ICU care and ventilatory support are needed to treat patients with Covid-19. Prompt and accurate clinical identification of SARS-CoV-2-infected patients at risk to have poor outcomes is an utmost priority. The aim of the study was to examine if the 2-point qSOFA threshold is an appropriate bedside clinical score for Covid-19 patients…