Discriminating between CPAP success and failure in COVID-19 patients with severe respiratory failure

 

Discriminating between CPAP success and failure in COVID-19 patients with severe respiratory failure

 

By: Pietro Arina, Beatrice Baso, Valeria Moro, Hemani Patel, Gareth Ambler on behalf of the UCL Critical Care COVID-19 Research Group

Intensive Care Medicine (2020) Published: 16 November 2020

 

Research letter

Continuous positive airways pressure (CPAP) treatment was used increasingly in the UK and elsewhere for coronavirus disease 2019 (COVID-19) to avoid the need for mechanical ventilation [1,2,3]. Early identification of patients benefitting from CPAP would assist decision making however we found that intensive care unit (ICU) admission respiratory parameters (rate, PaO2/FiO2 ratio) were poorly discriminatory. Using electronic healthcare records we retrospectively studied COVID-19 patients admitted to the University College London Hospital ICU between 8 March and 5 June 2020 in moderate-to-severe respiratory failure who received initial management with CPAP to see whether better prognosticators could be identified.

Comparison of demographic, clinical and biochemical parameters measured on ICU admission was made between patients adjudged CPAP success (hospital survival with CPAP alone) or failure (either death where CPAP was a ceiling of treatment, or need for mechanical ventilation regardless of hospital outcome). Requirement for other organ support was also compared. Patients managed on CPAP in non-ICU wards were excluded as detailed clinical and lab data were often lacking.

Of 108 within-hospital admissions, 93 (86%) received CPAP as initial respiratory failure management (median[IQR] PaO2/FiO2 ratio 13 [10–18] kPa) (Supplementary Fig. 1). Thirty-two (34%) were adjudged CPAP successes and 61 (66%) failures (14 deaths (23%) with CPAP as the ceiling of treatment, 47 (77%) requiring invasive ventilation of whom 26 died). Demographics and ICU admission values of respiratory rate, inspired oxygen concentration (FiO2) and PaO2/FiO2 ratio were similar between groups (Supplementary data). Admission values of C-reactive protein (CRP) (p < 0.0001), N Terminal-pro-B-type natriuretic peptide (NT-proBNP) (p < 0.001), troponin-T (p < 0.001) and D-dimers (p < 0.05) were significantly higher in CPAP failure patients (Fig. 1). Other organ support was only required for CPAP failure patients receiving invasive ventilation (46 vasopressors, 28 renal replacement therapy), but none for CPAP successes. At 6 h post-CPAP the PaO2/FiO2 ratio rose by 76.7% (37.9 to 99.8%) in CPAP success patients but only by 38.1% (−24.4 to 100.5) in the failure group (p = 0.015)…

Performance of the cuff leak test in adults in predicting post-extubation airway complications: a systematic review and meta-analysis

 

Performance of the cuff leak test in adults in predicting post-extubation airway complications: a systematic review and meta-analysis

 

by Akira Kuriyama, Jeffrey L. Jackson and Jun Kamei 

 

Critical Care volume 24, Article number: 640 (2020)

 

Background

Clinical practice guidelines recommend performing a cuff leak test in mechanically ventilated adults who meet extubation criteria to screen those at high risk for post-extubation stridor. Previous systematic reviews demonstrated excellent specificity of the cuff leak test but disagreed with respect to sensitivity. We conducted a systematic review and meta-analysis to assess the diagnostic accuracy of the cuff leak test for predicting post-extubation airway complications in intubated adult patients in critical care settings.

Methods

We searched Medline, EMBASE, Scopus, ISI Web of Science, the Cochrane Library for eligible studies from inception to March 16, 2020, without language restrictions. We included studies that examined the diagnostic accuracy of cuff leak test if post-extubation airway obstruction after extubation or reintubation was explicitly reported as the reference standard. Two authors in duplicate and independently assessed the risk of bias using the Quality Assessment for Diagnostic Accuracy Studies-2 tool. We pooled sensitivities and specificities using generalized linear mixed model approach to bivariate random-effects meta-analysis. Our primary outcomes were post-extubation airway obstruction and reintubation.

Results

We included 28 studies involving 4493 extubations. Three studies were at low risk for all QUADAS-2 risk of bias domains. The pooled sensitivity and specificity of cuff leak test for post-extubation airway obstruction were 0.62 (95% CI 0.49–0.73; I2 = 81.6%) and 0.87 (95% CI 0.82–0.90; I2 = 97.8%), respectively. The pooled sensitivity and specificity of the cuff leak test for reintubation were 0.66 (95% CI 0.46–0.81; I2 = 48.9%) and 0.88 (95% CI 0.83–0.92; I2 = 87.4%), respectively. Subgroup analyses suggested that the type of cuff leak test and length of intubation might be the cause of statistical heterogeneity of sensitivity and specificity, respectively, for post-extubation airway obstruction.

Conclusions

The cuff leak test has excellent specificity but moderate sensitivity for post-extubation airway obstruction. The high specificity suggests that clinicians should consider intervening in patients with a positive test, but the low sensitivity suggests that patients still need to be closely monitored post-extubation.

Weak anti-SARS-CoV-2 antibody response is associated with mortality in a Swedish cohort of COVID-19 patients in critical care

 

Weak anti-SARS-CoV-2 antibody response is associated with mortality in a Swedish cohort of COVID-19 patients in critical care

 

by Sana Asif, Robert Frithiof, Miklos Lipcsey, Bjarne Kristensen, Kjell Alving and Michael Hultström 

 

Critical Care volume 24, Article number: 639 (2020)

Research Letter

Profiling of the antibody responses to SARS-CoV-2 may be crucial to understand the immunological reaction and to design successful treatment strategies. Studies have confirmed the development of a typical antibody response to an acute viral infection in COVID-19 patients [1]. A robust generation and a dynamic pattern of IgA, IgM and IgG antibodies can be detected 2–3 weeks following the first symptoms of COVID-19 [2, 3]. An early robust antibody response in patients hospitalized with severe COVID-19 was reported in survivors, versus a weak antibody production in non-survivors [4, 5]. However, antibody responses to SARS-CoV-2 in critically ill patients is largely unknown.

We investigated the antibody response to SARS-Cov-2 Spike-1 protein in adult patients (n = 19) admitted to the intensive care unit (ICU) at a tertiary care hospital in Uppsala, Sweden. Plasma samples were collected at two different time points; (a) early, day 0–3 and (b) late, day 10–13, and concentrations of IgA, IgG and IgM antibodies were quantified by FluoroEnzymeImmunoassay (FEIA), Phadia AB, Uppsala, Sweden.

The median age of our cohort was 57 years, and 93% were males. The most common co-morbidities were obesity (93%), hypertension (42%) and diabetes mellitus type-2 (32%). The median COVID-19 day at ICU admission was 10 (6–14) days, the median length of ICU stay was 18 (11–38) days, and 30 days mortality was 21% (Table 1). In our cohort, a IgA, IgG and IgM antibody response could be detected as early as day 0–3 post-ICU admission, and this increase in antibodies was persistent up to day 10–13 (Fig. 1). A significant change in antibody concentrations over time was detected in patients who survived till day 30 in comparison with those who did not (Fig. 1). No associations were seen between antibody levels and patient age, or any other clinical or laboratory parameters. At both early and late timepoints, plasma concentrations of IgA, IgG and IgM antibodies tend to be higher in patients who survived compared to those who had died at 30 days (Fig. 1). This suggests that SARS-CoV-2 antibody response, similar to other virus illnesses, is important for virus protection and recovery. A limitation of the present dataset is the relatively low number of patients…

Spontaneous hemothorax in 4 COVID-19 ARDS patients on VV-ECMO revealing pulmonary artery aneurysms

 

Spontaneous hemothorax in 4 COVID-19 ARDS patients on VV-ECMO revealing pulmonary artery aneurysms

 

by Cyrielle Desnos, Samia Boussouar, Guillaume Hekimian, Alban Redheuil and Alain Combes 

 

Critical Care volume 24, Article number: 638 (2020)

 

COVID-19 pneumonia is a cause of severe ARDS. Its pathophysiology involves endothelial dysfunction and angiogenesis related to ACE-2 receptor, the host-cell receptor for SARS-CoV-2, expressed by endothelial cells, which may lead to thrombosis or hemorrhage [1].

This case series describes the presentation of COVID-19 patients who had unusual spontaneous hemothorax while on veno-venous extra corporeal membrane oxygenation (VV-ECMO) for severe ARDS. In accordance with French legislation, only non-opposition of patient’s surrogate for utilization of the deidentified data was obtained. The ICU database was registered with the national data protection authority (CNIL 1950673). From February to September 2020, 62 patients with confirmed COVID-19-related severe ARDS requiring VV-ECMO were transferred and treated in our tertiary care ICU, of whom 4 had spontaneous hemothorax.

Ages were 33, 63, 48 and 46 years; 2 patients were women. None of them had pulmonary embolism on previous CT angiography, and they had received continuous infusion of unfractionated heparin at high preventive dose according to international expert guidelines [2]. They were on VV-ECMO for 3, 9, 22 and 28 days at the time of the hemothorax onset. In all four patients, hemothorax was revealed by shock, both hemorrhagic and obstructive by compression of the mediastinum, requiring high doses of catecholamine and massive packed red blood cells transfusion. One patient experienced cardiac arrest shortly after shock onset, resuscitated after chest drainage. On chest CT scan, vascular lung abnormalities were very similar in the 4 patients, including peripheral medium and small pulmonary artery branches aneurysms, one of them also having renal and diaphragmatic artery aneurysms (Fig. 1). Three of the patients underwent salvage radioembolization, one of them survived to this episode without relapse, and hemothorax was fatal for the 3 others…

Effects of capillary refill time-vs. lactate-targeted fluid resuscitation on regional, microcirculatory and hypoxia-related perfusion parameters in septic shock: a randomized controlled trial

 

Effects of capillary refill time-vs. lactate-targeted fluid resuscitation on regional, microcirculatory and hypoxia-related perfusion parameters in septic shock: a randomized controlled trial

 

by Ricardo Castro, Eduardo Kattan, Giorgio Ferri, Ronald Pairumani, Emilio Daniel Valenzuela, Leyla Alegría, Vanessa Oviedo, Nicolás Pavez, Dagoberto Soto, Magdalena Vera, César Santis, Brusela Astudillo, María Alicia Cid, Sebastian Bravo, Gustavo Ospina-Tascón, Jan Bakker

 

Annals of Intensive Care volume 10, Article number: 150 (2020) 

 

Background

Persistent hyperlactatemia has been considered as a signal of tissue hypoperfusion in septic shock patients, but multiple non-hypoperfusion-related pathogenic mechanisms could be involved. Therefore, pursuing lactate normalization may lead to the risk of fluid overload. Peripheral perfusion, assessed by the capillary refill time (CRT), could be an effective alternative resuscitation target as recently demonstrated by the ANDROMEDA-SHOCK trial. We designed the present randomized controlled trial to address the impact of a CRT-targeted (CRT-T) vs. a lactate-targeted (LAC-T) fluid resuscitation strategy on fluid balances within 24 h of septic shock diagnosis. In addition, we compared the effects of both strategies on organ dysfunction, regional and microcirculatory flow, and tissue hypoxia surrogates.

Results

Forty-two fluid-responsive septic shock patients were randomized into CRT-T or LAC-T groups. Fluids were administered until target achievement during the 6 h intervention period, or until safety criteria were met. CRT-T was aimed at CRT normalization (≤ 3 s), whereas in LAC-T the goal was lactate normalization (≤ 2 mmol/L) or a 20% decrease every 2 h. Multimodal perfusion monitoring included sublingual microcirculatory assessment; plasma-disappearance rate of indocyanine green; muscle oxygen saturation; central venous-arterial pCO2 gradient/ arterial-venous O2 content difference ratio; and lactate/pyruvate ratio. There was no difference between CRT-T vs. LAC-T in 6 h-fluid boluses (875 [375–2625] vs. 1500 [1000–2000], p = 0.3), or balances (982[249–2833] vs. 15,800 [740–6587, p = 0.2]). CRT-T was associated with a higher achievement of the predefined perfusion target (62 vs. 24, p = 0.03). No significant differences in perfusion-related variables or hypoxia surrogates were observed.

Conclusions

CRT-targeted fluid resuscitation was not superior to a lactate-targeted one on fluid administration or balances. However, it was associated with comparable effects on regional and microcirculatory flow parameters and hypoxia surrogates, and a faster achievement of the predefined resuscitation target. Our data suggest that stopping fluids in patients with CRT ≤ 3 s appears as safe in terms of tissue perfusion.

Clinical Trials: ClinicalTrials.gov Identifier: NCT03762005 (Retrospectively registered on December 3rd 2018)

Corticosteroids in severe COVID-19: a critical view of the evidence

 

Corticosteroids in severe COVID-19: a critical view of the evidence

 

by Daniel De Backer, Elie Azoulay and Jean-Louis Vincent 

 

Critical Care volume 24, Article number: 627 (2020)

 

Since December 2019, SARS-CoV-2 has infected millions of people worldwide, causing excess deaths and a surge in demand for ICU beds. With no effective therapies against SARS-CoV-2, randomized trials of several potential therapeutic agents, including steroids, have been conducted. Although use of steroids in patients with ARDS [1] and severe viral pneumonia [2, 3] has been challenged, several arguments support the biological plausibility of steroid use in patients with severe COVID-19. First, autopsy studies in COVID-19 patients showed lymphocyte alveolitis, acute fibrinous injury and organizing pneumonia [4], which are all probably steroid-sensitive. Second, COVID-19 leads to activation of endothelial cells causing not only systemic inflammation but also microvascular thrombosis, pulmonary infarcts and venous thromboembolism [4, 5]. Admittedly, there are also arguments against steroid use. First, viral particles are often found at autopsy [4], and steroids may decrease viral clearance. Second, steroids only influence the inflammatory component of the inflammation–thrombosis–hypoxia interaction [6], suggesting that steroids may be less effective once thrombi have developed.

The RECOVERY trial compared administration of 6 mg/day dexamethasone for 10 days to usual care in 6425 hospitalized patients with SARS-CoV-2 infection. Survival was significantly higher in the dexamethasone-treated patients, especially in the subgroup of 1007 patients receiving invasive mechanical ventilation [7]. As a result of the RECOVERY findings, three further steroid trials, focusing on ICU patients, were stopped prematurely after inclusion of 384 [8], 299 [9] and 149 [10] patients, respectively. A meta-analysis of the available data concluded that administration of systemic steroids was associated with a decrease in 28-day mortality [11]. Nevertheless, although administration of steroids appears promising, several limitations must be considered when interpreting the results

Recommendations for hemodynamic monitoring for critically ill children—expert consensus statement issued by the cardiovascular dynamics section of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC)

Recommendations for hemodynamic monitoring for critically ill children—expert consensus statement issued by the cardiovascular dynamics section of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC)

 

by Yogen Singh, Javier Urbano Villaescusa, Eduardo M. da Cruz, Shane M. Tibby, Gabriella Bottari, Rohit Saxena, Marga Guillén, Jesus Lopez Herce, Matteo Di Nardo, Corrado Cecchetti, Joe Brierley, Willem de Boode and Joris Lemson

 

Critical Care volume 24, Article number: 620 (2020) 

 

Background

Cardiovascular instability is common in critically ill children. There is a scarcity of published high-quality studies to develop meaningful evidence-based hemodynamic monitoring guidelines and hence, with the exception of management of shock, currently there are no published guidelines for hemodynamic monitoring in children. The European Society of Paediatric and Neonatal Intensive Care (ESPNIC) Cardiovascular Dynamics section aimed to provide expert consensus recommendations on hemodynamic monitoring in critically ill children.

Methods

Creation of a panel of experts in cardiovascular hemodynamic assessment and hemodynamic monitoring and review of relevant literature—a literature search was performed, and recommendations were developed through discussions managed following a Quaker-based consensus technique and evaluating appropriateness using a modified blind RAND/UCLA voting method. The AGREE statement was followed to prepare this document.

Results

Of 100 suggested recommendations across 12 subgroups concerning hemodynamic monitoring in critically ill children, 72 reached “strong agreement,” 20 “weak agreement,” and 2 had “no agreement.” Six statements were considered as redundant after rephrasing of statements following the first round of voting. The agreed 72 recommendations were then coalesced into 36 detailing four key areas of hemodynamic monitoring in the main manuscript. Due to a lack of published evidence to develop evidence-based guidelines, most of the recommendations are based upon expert consensus.

Conclusions

These expert consensus-based recommendations may be used to guide clinical practice for hemodynamic monitoring in critically ill children, and they may serve as a basis for highlighting gaps in the knowledge base to guide further research in hemodynamic monitoring.

Early Detection of Patients at Risk of Developing a Post-Traumatic Stress Disorder After an ICU Stay*

 

Early Detection of Patients at Risk of Developing a Post-Traumatic Stress Disorder After an ICU Stay*

 

by Wawer, Emilie; Viprey, Marie; Floccard, Bernard; Saoud, Mohamed; Subtil, Fabien; Wafa, Hashim; Rheims, Elodie; Rimmelé, Thomas; Poulet, Emmanuel

 

Critical Care Medicine: November 2020 - Volume 48 - Issue 11 - p 1572-1579

 

Objectives:

To evaluate the diagnostic accuracy of the Impact Event Scale-Revisited assessed following ICU discharge to predict the emergence of post-traumatic stress disorder symptoms at 3 months. Design: Prospective cohort study. Setting: Three medical or surgical ICU of a French university hospital (Lyon, France). Patients: Patients greater than or equal to 18 years old, leaving ICU after greater than or equal to 2 nights of stay, between September 2017 and April 2018.

Interventions:

Patients completed the Impact Event Scale-Revisited and the Peritraumatic Dissociative Experiences Questionnaire within 8 days after ICU discharge and the Impact Event Scale-Revisited again at 3 months by phone. Patients having an Impact Event Scale-Revisited greater than or equal to 35 at 3 months were considered as having post-traumatic stress disorder symptoms.

Measurements and Main Results:

Among the 208 patients screened, 174 were included and 145 reassessed by phone at 3 months. Among the patients included at baseline, 43% presented symptoms of acute stress. At 3 months, 13% had an Impact Event Scale-Revisited greater than or equal to 35 and 17% had a score between 12 and 34. Regarding the performance of the Impact Event Scale-Revisited performed within 8 days after the ICU discharge to predict post-traumatic stress disorder symptoms at 3 months, the area under the curve was 0.90 (95% CI, 0.80–0.99), and an Impact Event Scale-Revisited greater than or equal to 12 had a sensitivity of 90%, a specificity of 71%, a positive predictive value of 32%, and a negative predictive value of 98%. History of anxiety disorder odds ratio = 3.7 (95% CI, 1.24–11.05; p = 0.02) and Impact Event Scale-Revisited greater than or equal to 12 odds ratio = 16.57 (95% CI, 3.59–76.46; p < 0.001) were identified as risk factors for post-traumatic stress disorder symptoms.

Conclusions: Impact Event Scale-Revisited assessed at ICU discharge has a good ability for the detection of patients at risk of developing post-traumatic stress disorder symptoms. Patients with history of anxiety disorder and those presenting acute stress symptoms at ICU discharge are more at risk to develop post-traumatic stress disorder symptoms.

Gut-liver crosstalk in sepsis-induced liver injury

 

Gut-liver crosstalk in sepsis-induced liver injury

 

by Jian Sun, Jingxiao Zhang, Xiangfeng Wang, Fuxi Ji, Claudio Ronco, Jiakun Tian and Yongjie Yin 

 

Critical Care  volume 24, Article number: 614 (2020) 

 

Sepsis is characterized by a dysregulated immune response to infection leading to life-threatening organ dysfunction. Sepsis-induced liver injury is recognized as a powerful independent predictor of mortality in the intensive care unit. During systemic infections, the liver regulates immune defenses via bacterial clearance, production of acute-phase proteins (APPs) and cytokines, and metabolic adaptation to inflammation. Increased levels of inflammatory cytokines and impaired bacterial clearance and disrupted metabolic products can cause gut microbiota dysbiosis and disruption of the intestinal mucosal barrier. Changes in the gut microbiota play crucial roles in liver injury during sepsis. Bacterial translocation and resulting intestinal inflammation lead to a systemic inflammatory response and acute liver injury. The gut-liver crosstalk is a potential target for therapeutic interventions. This review analyzes the underlying mechanisms for the gut-liver crosstalk in sepsis-induced liver injury.

High-Flow Nasal Oxygen in Coronavirus Disease 2019 Patients With Acute Hypoxemic Respiratory Failure: A Multicenter, Retrospective Cohort Study*

 

High-Flow Nasal Oxygen in Coronavirus Disease 2019 Patients With Acute Hypoxemic Respiratory Failure: A Multicenter, Retrospective Cohort Study*

 

by Xia, Jingen; Zhang, Yi; Ni, Lan; Chen, Lei; Zhou, Changzhi; Gao, Chang; Wu, Xiaojing; Duan, Jun; Xie, Jungang; Guo, Qiang; Zhao, Jianping; Hu, Yi; Cheng, Zhenshun; Zhan, Qingyuan

Critical Care Medicine: November 2020 - Volume 48 - Issue 11 - p e1079-e1086

Objectives:  

An ongoing outbreak of coronavirus disease 2019 is spreading globally. Acute hypoxemic respiratory failure is the most common complication of coronavirus disease 2019. However, the clinical effectiveness of early high-flow nasal oxygen treatment in patients with coronavirus disease 2019 with acute hypoxemic respiratory failure has not been explored. This study aimed to analyze the effectiveness of high-flow nasal oxygen treatment and to identify the variables predicting high-flow nasal oxygen treatment failure in coronavirus disease 2019 patients with acute hypoxemic respiratory failure.

Design:

A multicenter, retrospective cohort study. Setting: Three tertiary hospitals in Wuhan, China. Patients: Forty-three confirmed coronavirus disease 2019 adult patients with acute hypoxemic respiratory failure treated with high-flow nasal oxygen. Interventions: None.

Measurements and Main Results:

Mean age of the enrolled patients was 63.0 ± 9.7 years; female patients accounted for 41.9%. High-flow nasal oxygen failure (defined as upgrading respiratory support to positive pressure ventilation or death) was observed in 20 patients (46.5%), of which 13 (30.2%) required endotracheal intubation. Patients with high-flow nasal oxygen success had a higher median oxygen saturation (96.0% vs 93.0%; p < 0.001) at admission than those with high-flow nasal oxygen failure. High-flow nasal oxygen failure was more likely in patients who were older (p = 0.030) and male (p = 0.037), had a significant increase in respiratory rate and a significant decrease in the ratio of oxygen saturation/Fio2 to respiratory rate index within 3 days of high-flow nasal oxygen treatment. In a multivariate logistic regression analysis model, male and lower oxygen saturation at admission remained independent predictors of high-flow nasal oxygen failure. The hospital mortality rate of the cohort was 32.5%; however, the hospital mortality rate in patients with high-flow nasal oxygen failure was 65%.

Conclusions:

High-flow nasal oxygen may be effective for treating coronavirus disease 2019 patients with mild to moderate acute hypoxemic respiratory failure. However, high-flow nasal oxygen failure was associated with a poor prognosis. Male and lower oxygenation at admission were the two strong predictors of high-flow nasal oxygen failure.