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…

Tuesday, 25 February 2020

The global survival rate among adult out-of-hospital cardiac arrest patients who received cardiopulmonary resuscitation: a systematic review and meta-analysis

by Shijiao Yan, Yong Gan, Nan Jiang, Rixing Wang, Yunqiang Chen, Zhiqian Luo, Qiao Zong, Song Chen and Chuanzhu Lv

Critical Care volume 24, Article number: 61 (2020) Published: 22 February 2020

To quantitatively summarize the available epidemiological evidence on the survival rate of out-of-hospital cardiac arrest (OHCA) patients who received cardiopulmonary resuscitation (CPR).
We systematically searched the PubMed, Embase, and Web of Science databases, and the references of retrieved articles were manually reviewed to identify studies reporting the outcome of OHCA patients who received CPR. The overall incidence and outcome of OHCA were assessed using a random-effects meta-analysis.
A total of 141 eligible studies were included in this meta-analysis. The pooled incidence of return of spontaneous circulation (ROSC) was 29.7% (95% CI 27.6–31.7%), the rate of survival to hospital admission was 22.0% (95% CI 20.7–23.4%), the rate of survival to hospital discharge was 8.8% (95% CI 8.2–9.4%), the pooled 1-month survival rate was 10.7% (95% CI 9.1–13.3%), and the 1-year survival rate was 7.7% (95% CI 5.8–9.5%). Subgroup analysis showed that survival to hospital discharge was more likely among OHCA patients whose cardiac arrest was witnessed by a bystander or emergency medical services (EMS) (10.5%; 95% CI 9.2–11.7%), who received bystander CPR (11.3%, 95% CI 9.3–13.2%), and who were living in Europe and North America (Europe 11.7%; 95% CI 10.5–13.0%; North America: 7.7%; 95% CI 6.9–8.6%). The survival to discharge (8.6% in 1976–1999 vs. 9.9% in 2010–2019), 1-month survival (8.0% in 2000–2009 vs. 13.3% in 2010–2019), and 1-year survival (8.0% in 2000–2009 vs. 13.3% in 2010–2019) rates of OHCA patients who underwent CPR significantly increased throughout the study period. The Egger’s test did not indicate evidence of publication bias for the outcomes of OHCA patients who underwent CPR.
The global survival rate of OHCA patients who received CPR has increased in the past 40 years. A higher survival rate post-OHCA is more likely among patients who receive bystander CPR and who live in Western countries.

Biomarkers of Delirium Duration and Delirium Severity in the ICU*

by Khan, Babar A.; Perkins, Anthony J.; Prasad, Nagendra K.; Shekhar, Anantha; Campbell, Noll L.; Gao, Sujuan; Wang, Sophia; Khan, Sikandar H.; Marcantonio, Edward R.; Twigg, Homer L. III; Boustani, Malaz A.

Objectives: Both delirium duration and delirium severity are associated with adverse patient outcomes. Serum biomarkers associated with delirium duration and delirium severity in ICU patients have not been reliably identified. We conducted our study to identify peripheral biomarkers representing systemic inflammation, impaired neuroprotection, and astrocyte activation associated with delirium duration, delirium severity, and in-hospital mortality.
Design: Observational study.
Setting: Three Indianapolis hospitals.
Patients: Three-hundred twenty-one critically ill delirious patients.
Interventions: None.
Measurements and Main Results: We analyzed the associations between biomarkers collected at delirium onset and delirium-/coma-free days assessed through Richmond Agitation-Sedation Scale/Confusion Assessment Method for the ICU, delirium severity assessed through Confusion Assessment Method for the ICU-7, and in-hospital mortality. After adjusting for age, gender, Acute Physiology and Chronic Health Evaluation II score, Charlson comorbidity score, sepsis diagnosis and study intervention group, interleukin-6, -8, and -10, tumor necrosis factor-α, C-reactive protein, and S-100β levels in quartile 4 were negatively associated with delirium-/coma-free days by 1 week and 30 days post enrollment. Insulin-like growth factor-1 levels in quartile 4 were not associated with delirium-/coma-free days at both time points. Interleukin-6, -8, and -10, tumor necrosis factor-α, C-reactive protein, and S-100β levels in quartile 4 were also associated with delirium severity by 1 week. At hospital discharge, interleukin-6, -8, and -10 retained the association but tumor necrosis factor-α, C-reactive protein, and S-100β lost their associations with delirium severity. Insulin-like growth factor-1 levels in quartile 4 were not associated with delirium severity at both time points. Interleukin-8 and S-100β levels in quartile 4 were also associated with higher in-hospital mortality. Interleukin-6 and -10, tumor necrosis factor-α, and insulin-like growth factor-1 were not found to be associated with in-hospital mortality.
Conclusions: Biomarkers of systemic inflammation and those for astrocyte and glial activation were associated with longer delirium duration, higher delirium severity, and in-hospital mortality. Utility of these biomarkers early in delirium onset to identify patients at a higher risk of severe and prolonged delirium, and delirium related complications during hospitalization needs to be explored in future studies.

Critical care response to a hospital outbreak of the 2019-nCoV infection in Shenzhen, China

by Yong Liu, Jinxiu Li and Yongwen Feng 

Critical Care volume 24, Article number: 56 (2020)

Beginning at early December 2019, there is an outbreak of a novel 2019-nCoV in Wuhan, China. Then, Public Health Emergency of International Concern (PHEIC) was declared on 30 January 2020, by the World Health Organization (WHO) Emergency Committee. The 2019-nCoV pandemic could lead to an influx of critically ill into the already strained hospital systems in mainland China. Dealing with the pandemic requires a robust hospital- and city-wide command and control structure that could make quick and informed decisions among Chinese hospitals. We recommend that a proper plan can enable the local government, healthcare systems, hospitals, and healthcare workers to better cope with such public eventuality. The response should be flexible and adjustable according to the size of the population impacted.

Humanizing Intensive Care: Toward a Human-Centered Care ICU Model

by Nin Vaeza, Nicolas; Martin Delgado, María Cruz; Heras La Calle, Gabriel 

“If you could choose, how would you like the Intensive Care Units (ICUs) to be?” The Humanization of Intensive Care movement (Proyecto HU-CI) arose after we asked this simple question in our blog, receiving suggestions from more 10,000 people (1). Created in Spain on February 2014, the Humanization of Intensive Care movement is an international research project that seeks, using evidence-based medicine, to answer that same question, thus creating a paradigm shift in the way we deliver our care toward a more friendly and human-centered model (2). Although many may be surprised and feel a contradiction toward this humanistic model, is an essential skill in health professionals that should have never been lost. When professionals are face with the reality of being patients or a family member of critically ill patient, it is then, when they appreciate how it works. “Yet many professionals cite lack of humanistic care as a cause for burnout, an epidemic among health professions today” (3).
Displaying kindness and concern for all the individuals that are part of the healthcare environment, not only patients and its families, is a necessity and the path toward building an excellent healthcare system. We will not be able to cure all people, but surely, we can improve the care we provide by focusing on the dignity of people…

Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Cardiovascular, Endocrine, Hematologic, Pulmonary, and Renal Considerations

To develop evidence-based recommendations for clinicians caring for adults with acute or acute on chronic liver failure in the ICU.
The guideline panel comprised 29 members with expertise in aspects of care of the critically ill patient with liver failure and/or methodology. The Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy were followed throughout. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development.
The panel was divided into nine subgroups: cardiovascular, hematology, pulmonary, renal, endocrine and nutrition, gastrointestinal, infection, perioperative, and neurology.
We developed and selected population, intervention, comparison, and outcomes questions according to importance to patients and practicing clinicians. For each population, intervention, comparison, and outcomes question, we conducted a systematic review aiming to identify the best available evidence, statistically summarized the evidence whenever applicable, and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements.
Measurements and Main Results: 
In this article, we report 29 recommendations (from 30 population, intervention, comparison, and outcomes questions) on the management acute or acute on chronic liver failure in the ICU, related to five groups (cardiovascular, hematology, pulmonary, renal, and endocrine). Overall, six were strong recommendations, 19 were conditional recommendations, four were best-practice statements, and in two instances, the panel did not issue a recommendation due to insufficient evidence.
Multidisciplinary international experts were able to formulate evidence-based recommendations for the management acute or acute on chronic liver failure in the ICU, acknowledging that most recommendations were based on low-quality indirect evidence.

The exsecutive summary can be found here: https://journals.lww.com/ccmjournal/Fulltext/2020/03000/Guidelines_for_the_Management_of_Adult_Acute_and.17.aspx

Neurally adjusted ventilatory assist vs. pressure support to deliver protective mechanical ventilation in patients with acute respiratory distress syndrome: a randomized crossover trial

by Fabia Diniz-Silva, Henrique T. Moriya, Adriano M. Alencar, Marcelo B. P. Amato, Carlos R. R. Carvalho and Juliana C. Ferreira

Annals of Intensive Care volume 10, Article number: 18 (2020)

Protective mechanical ventilation is recommended for patients with acute respiratory distress syndrome (ARDS), but it usually requires controlled ventilation and sedation. Using neurally adjusted ventilatory assist (NAVA) or pressure support ventilation (PSV) could have additional benefits, including the use of lower sedative doses, improved patient–ventilator interaction and shortened duration of mechanical ventilation. We designed a pilot study to assess the feasibility of keeping tidal volume (VT) at protective levels with NAVA and PSV in patients with ARDS.
We conducted a prospective randomized crossover trial in five ICUs from a university hospital in Brazil and included patients with ARDS transitioning from controlled ventilation to partial ventilatory support. NAVA and PSV were applied in random order, for 15 min each, followed by 3 h in NAVA. Flow, peak airway pressure (Paw) and electrical activity of the diaphragm (EAdi) were captured from the ventilator, and a software (Matlab, Mathworks, USA), automatically detected inspiratory efforts and calculated respiratory rate (RR) and VT. Asynchrony events detection was based on waveform analysis.
We randomized 20 patients, but the protocol was interrupted for five (25%) patients for whom we were unable to maintain VT below 6.5 mL/kg in PSV due to strong inspiratory efforts and for one patient for whom we could not detect EAdi signal. For the 14 patients who completed the protocol, VT was 5.8 ± 1.1 mL/kg for NAVA and 5.6 ± 1.0 mL/kg for PSV (p = 0.455) and there were no differences in RR (24 ± 7 for NAVA and 23 ± 7 for PSV, p = 0.661). Paw was greater in NAVA (21 ± 3 cmH2O) than in PSV (19 ± 3 cmH2O, p = 0.001). Most patients were under continuous sedation during the study. NAVA reduced triggering delay compared to PSV (p = 0.020) and the median asynchrony Index was 0.7% (0–2.7) in PSV and 0% (0–2.2) in NAVA (p = 0.6835).
It was feasible to keep VT in protective levels with NAVA and PSV for 75% of the patients. NAVA resulted in similar VT, RR and Paw compared to PSV. Our findings suggest that partial ventilatory assistance with NAVA and PSV is feasible as a protective ventilation strategy in selected ARDS patients under continuous sedation.
Trial registration ClinicalTrials.gov (NCT01519258). Registered 26 January 2012, https://clinicaltrials.gov/ct2/show/NCT01519258

Investigating Swallowing and Tracheostomy Following Critical Illness: A Scoping Review

by Skoretz, Stacey A.; Riopelle, Stephanie J.; Wellman, Leslie; Dawson, Camilla 

Objectives: Tracheostomy and dysphagia often coexist during critical illness; however, given the patient’s medical complexity, understanding the evidence to optimize swallowing assessment and intervention is challenging. The objective of this scoping review is to describe and explore the literature surrounding swallowing and tracheostomy in the acute care setting.
Data Sources: Eight electronic databases were searched from inception to May 2017 inclusive, using a search strategy designed by an information scientist. We conducted manual searching of 10 journals, nine gray literature repositories, and forward and backward citation chasing.
Study Selection: Two blinded reviewers determined eligibility according to inclusion criteria: English-language studies reporting on swallowing or dysphagia in adults (≥ 17 yr old) who had undergone tracheostomy placement while in acute care. Patients with head and/or neck cancer diagnoses were excluded.
Data Extraction: We extracted data using a form designed a priori and conducted descriptive analyses.
Data Synthesis: We identified 6,396 citations, of which 725 articles were reviewed and 85 (N) met inclusion criteria. We stratified studies according to content domains with some featuring in multiple categories: dysphagia frequency (n = 38), swallowing physiology (n = 27), risk factors (n = 31), interventions (n = 21), and assessment comparisons (n = 12) and by patient etiology. Sample sizes (with tracheostomy) ranged from 10 to 3,320, and dysphagia frequency ranged from 11% to 93% in studies with consecutive sampling. Study design, sampling method, assessment methods, and interpretation approach varied significantly across studies.
Conclusions: The evidence base surrounding this subject is diverse, complicated by heterogeneous patient selection methods, design, and reporting. We suggest ways the evidence base may be developed.

Higher glycemic variability within the first day of ICU admission is associated with increased 30-day mortality in ICU patients with sepsis

by Wen-Cheng Chao, Chien-Hua Tseng, Chieh-Liang Wu, Sou-Jen Shih, Chi-Yuan Yi and Ming-Cheng Chan 

Annals of Intensive Care volume 10, Article number: 17 (2020)

High glycemic variability (GV) is common in critically ill patients; however, the prevalence and mortality association with early GV in patients with sepsis remains unclear.
This retrospective cohort study was conducted in a medical intensive care unit (ICU) in central Taiwan. Patients in the ICU with sepsis between January 2014 and December 2015 were included for analysis. All of these patients received protocol-based management, including blood sugar monitoring every 2 h for the first 24 h of ICU admission. Mean amplitude of glycemic excursions (MAGE) and coefficient of variation (CoV) were used to assess GV.
A total of 452 patients (mean age 71.4 ± 14.7 years; 76.7% men) were enrolled for analysis. They were divided into high GV (43.4%, 196/452) and low GV (56.6%, 256/512) groups using MAGE 65 mg/dL as the cut-off point. Patients with high GV tended to have higher HbA1c (6.7 ± 1.8% vs. 5.9 ± 0.9%, p < 0.01) and were more likely to have diabetes mellitus (DM) (50.0% vs. 23.4%, p < 0.01) compared with those in the low GV group. Kaplan–Meier analysis showed that a high GV was associated with increased 30-day mortality (log-rank test, p = 0.018). The association remained strong in the non-DM (log-rank test, p = 0.035), but not in the DM (log-rank test, p = 0.254) group. Multivariate Cox proportional hazard regression analysis identified that high APACHE II score (adjusted hazard ratio (aHR) 1.045, 95% confidence interval (CI) 1.013–1.078), high serum lactate level at 0 h (aHR 1.009, 95% CI 1.003–1.014), having chronic airway disease (aHR 0.478, 95% CI 0.302–0.756), high mean day 1 glucose (aHR 1.008, 95% CI 1.000–1.016), and high MAGE (aHR 1.607, 95% CI 1.008–2.563) were independently associated with increased 30-day mortality. The association with 30-day mortality remained consistent when using CoV to assess GV.
We found that approximately 40% of the septic patients had a high early GV, defined as MAGE > 65 mg/dL. Higher GV within 24 h of ICU admission was independently associated with increased 30-day mortality. These findings highlight the need to monitor GV in septic patients early during an ICU admission.

Nutrition therapy in critical illness: a review of the literature for clinicians

by Kate J. Lambell, Oana A. Tatucu-Babet, Lee-anne Chapple, Dashiell Gantner and Emma J. Ridley

Critical Care volume 24, Article number: 35 (2020)

Nutrition therapy during critical illness has been a focus of recent research, with a rapid increase in publications accompanied by two updated international clinical guidelines. However, the translation of evidence into practice is challenging due to the continually evolving, often conflicting trial findings and guideline recommendations. This narrative review aims to provide a comprehensive synthesis and interpretation of the adult critical care nutrition literature, with a particular focus on continuing practice gaps and areas with new data, to assist clinicians in making practical, yet evidence-based decisions regarding nutrition management during the different stages of critical illness.

Novel coronavirus infection during the 2019–2020 epidemic: preparing intensive care units—the experience in Sichuan Province, China

Intensive Care Medicine volume 46, pages 357–360(2020)

Up to 31 January 2020, there have been 9811 officially reported confirmed cases of 2019-novel coronavirus (nCoV) infection in China since the epidemic began in December 2019 (updated data available at https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6).

With the rapid transmission, the epidemic has spread throughout the country, and 177 cases have been reported in Sichuan Province. As nCoV infection is a highly contagious disease with high mortality (3–15%) [1,2,3] and West China Hospital (WCH) is the largest hospital in the southwest of China and the referral medical center in Sichuan Province, it is our responsibility to prepare for admission of additional critically ill patients as a matter of emergency. We have held several expert meetings and have reviewed the related literature to develop a plan to respond to the epidemic [45]. The purpose of the plan is to enable us to provide the maximum level of care to critically ill patients while ensuring the protection of medical staff…

Ventilatory support and mechanical properties of the fibrotic lung acting as a “squishy ball”

by Alessandro Marchioni, Roberto Tonelli, Giulio Rossi, Paolo Spagnolo, Fabrizio Luppi, Stefania Cerri, Elisabetta Cocconcelli, Maria Rosaria Pellegrino, Riccardo Fantini, Luca Tabbì, Ivana Castaniere, Lorenzo Ball, Manu L. N. G. Malbrain, Paolo Pelosi and Enrico Clini

Annals of Intensive Care volume 10, Article number: 13 (2020)

Protective ventilation is the cornerstone of treatment of patients with the acute respiratory distress syndrome (ARDS); however, no studies have yet established the best ventilatory strategy to adopt when patients with acute exacerbation of interstitial lung disease (AE-ILD) are admitted to the intensive care unit. Due to the severe impairment of the respiratory mechanics, the fibrotic lung is at high risk of developing ventilator-induced lung injury, regardless of the lung fibrosis etiology. The purpose of this review is to analyze the effects of mechanical ventilation in AE-ILD and to increase the knowledge on the characteristics of fibrotic lung during artificial ventilation, introducing the concept of “squishy ball lung”. The role of positive end-expiratory pressure is discussed, proposing a “lung resting strategy” as opposed to the “open lung approach”. The review also discusses the practical management of AE-ILD patients discussing illustrative clinical cases.

Methylnaltrexone for the treatment of opioid-induced constipation and gastrointestinal stasis in intensive care patients. Results from the MOTION trial

Constipation can be a significant problem in critically unwell patients, associated with detrimental outcomes. Opioids are thought to contribute to the mechanism of bowel dysfunction. We tested if methylnaltrexone, a pure peripheral mu-opioid receptor antagonist, could reverse opioid-induced constipation.
The MOTION trial is a multi-centre, double blind, randomised placebo-controlled trial to investigate whether methylnaltrexone alleviates opioid-induced constipation (OIC) in critical care patients. Eligibility criteria included adult ICU patients who were mechanically ventilated, receiving opioids and were constipated (had not opened bowels for a minimum 48 h) despite prior administration of regular laxatives as per local bowel management protocol. The primary outcome was time to significant rescue-free laxation. Secondary outcomes included gastric residual volume, tolerance of enteral feeds, requirement for rescue laxatives, requirement for prokinetics, average number of bowel movements per day, escalation of opioid dose due to antagonism/reversal of analgesia, incidence of ventilator-associated pneumonia, incidence of diarrhoea and Clostridium difficile infection and finally 28 day, ICU and hospital mortality.
A total of 84 patients were enrolled and randomized (41 to methylnaltrexone and 43 to placebo). The baseline demographic characteristics of the two groups were generally well balanced. There was no significant difference in time to rescue-free laxation between the groups (Hazard ratio 1.42, 95% CI 0.82–2.46, p = 0.22). There were no significant differences in the majority of secondary outcomes, particularly days 1–3. However, during days 4–28, there were fewer median number of bowel movements per day in the methylnaltrexone group, (p = 0.01) and a greater incidence of diarrhoea in the placebo group (p = 0.02). There was a marked difference in mortality between the groups, with ten deaths in the methylnaltrexone group and two in the placebo group during days 4–28 (p = 0.007).
We found no evidence to support the addition of methylnaltrexone to regular laxatives for the treatment of opioid-induced constipation in critically ill patients; however, the confidence interval was wide and a clinically important difference cannot be excluded.

Effects of endovascular and surface cooling on resuscitation in patients with cardiac arrest and a comparison of effectiveness, stability, and safety: a systematic review and meta-analysis

by Xueli Liao, Ziyu Zhou, Manhong Zhou, Hui Tang, Menglong Feng, Bujin Kou, Ni Zhu, Futuan Liao and Liaozhang Wu

Critical Care volume 24, Article number: 27 (2020)

This study conducted a meta-analysis to assess the effectiveness, stability, and safety of mild therapeutic hypothermia (TH) induced by endovascular cooling (EC) and surface cooling (SC) and its effect on ICU, survival rate, and neurological function integrity in adult CA patients.
We developed inclusion criteria, intervention protocols, results, and data collection. The results included outcomes during target temperature management as well as ICU stay, survival rate, and neurological functional integrity. The characteristics of the included population and each study were analyzed.
Four thousand nine hundred thirteen participants met the inclusion criteria. Those receiving EC had a better cooling efficiency (cooling rates MD = 0.31[0.13, 0.50], p < 0.01; induced cooling times MD = − 90.45[− 167.57, − 13.33], p = 0.02; patients achieving the target temperature RR = 1.60[1.19, 2.15], p < 0.01) and thermal stability during the maintenance phase (maintenance time MD = 2.35[1.22, 3.48], p < 0.01; temperature fluctuation MD = − 0.68[− 1.03, − 0.33], p < 0.01; overcooling RR = 0.33[0.23, 0.49], p < 0.01). There were no differences in ICU survival rate (RR = 1.22[0.98, 1.52], p = 0.07, I2 = 0%) and hospital survival rate (RR = 1.02 [0.96, 1.09], p = 0.46, I2 = 0%), but EC reduced the length of stay in ICU (MD = − 1.83[− 3.45, − 0.21], p = 0.03, I2 = 49%) and improved outcome of favorable neurological function at discharge (RR = 1.15[1.04, 1.28], p < 0.01, I2 = 0%). EC may delay the hypothermia initiation time, and there was no significant difference between the two cooling methods in the time from the start of patients’ cardiac arrest to achieve the target temperature (MD = − 46.64[− 175.86, 82.58]). EC was superior to non-ArcticSun in terms of cooling efficiency. Although there was no statistical difference in ICU survival rate, ICU length of stay, and hospitalization survival rate, in comparison to non-ArcticSun, EC improved rates of neurologically intact survival (RR = 1.16 [1.01, 1.35], p = 0.04, I2 = 0%).
Among adult patients receiving cardiopulmonary resuscitation, although there is no significant difference between the two cooling methods in the time from the start of cardiac arrest to achieve the target temperature, the faster cooling rate and more stable cooling process in EC shorten patients’ ICU hospitalization time and help more patients obtain good neurological prognosis compared with patients receiving SC. Meanwhile, although EC has no significant difference in patient outcomes compared with ArcticSun, EC has improved rates of neurologically intact survival.

Thursday, 23 January 2020

Timing of Tracheostomy in Pediatric Patients: A Systematic Review and Meta-Analysis*

by Abdelaal Ahmed Mahmoud M. Alkhatip, Ahmed; Younis, Mohamed; Jamshidi, Negar; Hussein, Hazem A; Farag, Ehab; Hamza, Mohamed K.; Bahr, Mahmoud H.; Goda Ahmed, Ahmed; Sallam, Amr M.; Mohamed, Hassan; Elayashy, Mohamed; Hosny, Hisham; Yassin, Hany M.; Abdelhaq, Mohamed; Elramely, Mohamed A.; Reeves, David; Mills, Kerry E.; Kamal, Ahmed M.; Zakaria, Dina

Objectives: Tracheostomy is a very common clinical intervention in critically ill adult patients. The indications for tracheostomy procedures in pediatric patients with complex conditions have increased dramatically in recent years, but there are currently no guidelines on the optimal timing of tracheostomy in pediatric patients undergoing prolonged ventilation.
 Data Sources: We performed a systematic search of the existing literature in MEDLINE via PubMed and Embase databases and the Cochrane Library to identify clinical trials, observational studies, and cohort studies that compare early and late tracheostomy in children. The date of the last search was August 27, 2018. Included articles were subjected to manual searching.
Study Selection: Studies in mechanically ventilated children that compared early with late tracheostomy were included.
Data Extraction: Data were extracted into a spreadsheet and copied into Review Manager 5.3 (The Cochrane Collaboration, Copenhagen, Denmark).
Data Synthesis: Data were meta-analyzed using an inverse variance, random effects model. Continuous outcomes were calculated as mean differences with 95% CIs, and dichotomous outcomes were calculated as Mantel-Haenszel risk ratios with 95% CIs. We included eight studies (10 study arms). These studies were all retrospective cohort studies. Early tracheostomy was associated with significant reductions in mortality, days on mechanical ventilation, and length of intensive care and total hospital stay, although the lack of randomized, controlled trials limits the validity of these findings. Although variance was imputed for some studies, these conclusions did not change after removing these studies from the analysis.
Conclusions: In children on mechanical ventilation, early tracheostomy may improve important medical outcomes. However, our data demonstrate the urgent need for high-quality, randomized controlled trials in the pediatric population.