LETTER: “It was a nightmare until I saw my wife”: the importance of family presence for patients with COVID-19 hospitalized in the ICU

 

LETTER: “It was a nightmare until I saw my wife”: the importance of family presence for patients with COVID-19 hospitalized in the ICU

 

Nancy Kentish-Barnes, Philonille Degos, Clémence Viau, Frédéric Pochard & Elie Azoulay 

Intensive Care Medicine Published: 11 May 2021

 

During the initial pandemic of coronavirus disease 2019 (COVID-19), visits in the intensive care unit (ICU) were either banned or highly restricted. Consequently, family members and patients were often separated from each other. Quantitative and qualitative research has shown that this restriction was an extremely difficult and even harmful experience for both family members and ICU clinicians [1, 2]. Lack of visits is a well-known risk factor for delirium [3] and studies have shown that extending visiting policies can strongly reduce both the incidence of delirium and its length [4]. In this qualitative pilot study that included semi-structured interviews with 12 ICU survivors of the COVID-19 9–10 months after their discharge, we sought to better understand the experience of patients’ hospitalization in the ICU during the first wave of the pandemic (Supplemental material). Qualitative analysis provides an in-depth insight into the relationship between the patient and his loved-one in the ICU, although our data may not precisely translate how patients actually felt in the moment, given a potential for recall bias and the effect of media exposure between the ICU stay and the interviews.

Most patients (9/12) reported having no memories of their ICU admission: their first memory was gaining consciousness after their coma (due to sedation for mechanical ventilation). Patients described being agitated and confused, not knowing whether their dreams were reality or not (Table 1, Q1). Many patients described terrifying dreams during which they thought they were going to die (Table 1, Q2). ICU delirium is well described and can cause patients to have horrifying, violent hallucinations to the point where they feel that they are going crazy. In our study, patients described not knowing where they were and having no familiar faces to reassure them (Table 1, Q3).

If not now, when? A clinical perspective on the unprecedented challenges facing ICUs during the COVID-19 pandemic

If not now, when? A clinical perspective on the unprecedented challenges facing ICUs during the COVID-19 pandemic

 

Intensive Care Medicine, Editorial: Published: 11 May 2021

Intensive care units (ICUs) worldwide continue to struggle with the massive influx of patients with critical illness associated to coronavirus disease 2019 (COVID-19). Their capacity is overwhelmed and there is clearly a need to act to implement a crisis standard of care, in an attempt to mitigate disparities in access to intensive care. The process of characterizing the natural progression of a disease and the pathophysiological differences between different categories of critically ill patients requires many years of in-depth study. And even when such characterization is available to help us make clinical judgments, we, as intensivists, continue to face challenges in achieving consensus and implementing critical care guidelines. The COVID-19 pandemic has led to a complete change in the way we conduct research, interpret results, and make recommendations. Over the past year, immediacy has become the dominant theme, favored over quality.

One particularly important feature of the current emergency has been the change we are seeing in the type of patients being admitted to ICUs. At the start of the COVID-19 pandemic, reports indicated that the disease mostly affected older adults and that young people were more likely to have milder disease. At that time, we were warned that our main focus should be to reduce infection and subsequent transmission to persons at higher risk of severe illness. Over time, however, this global consensus started to change. According to data from epidemiological teams at the Centers for Disease Control and Prevention in the United States, people under the age of 30 accounted for more than 20% of COVID-19 cases over the summer of 2020. This trend was subsequently validated, as reported in a study from Brazil by Kurtz et al. published in this issue of Intensive Care Medicine…

The Association Between Antibiotic Delay Intervals and Hospital Mortality Among Patients Treated in the Emergency Department for Suspected Sepsis*

 

The Association Between Antibiotic Delay Intervals and Hospital Mortality Among Patients Treated in the Emergency Department for Suspected Sepsis*

by Taylor, Stephanie Parks; Anderson, William E.; Beam, Kent; Taylor, Brice; Ellerman, Justin; Kowalkowski, Marc A

Critical Care Medicine: May 2021 - Volume 49 - Issue 5 - p 741-747

OBJECTIVES: 

Rapid delivery of antibiotics is a cornerstone of sepsis therapy, although time targets for specific components of antibiotic delivery are unknown. We quantified time intervals comprising the task of antibiotic delivery and evaluated the association between interval delays and hospital mortality among patients treated in the emergency department for suspected sepsis.

DESIGN: 

Retrospective cohort.

SETTING: 

Twelve hospitals in Southeastern United States from 2014 to 2017.

PATIENTS: 

Twenty-four thousand ninety-three encounters among 20,026 adults with suspected sepsis in 12 emergency departments.

MEASUREMENTS AND MAIN RESULTS: 

We divided antibiotic administration into two intervals: time from emergency department triage to antibiotic order (recognition delay) and time from antibiotic order to infusion (administration delay). We used generalized linear mixed models to evaluate associations between these intervals and hospital mortality. Median time from emergency department triage to antibiotic administration was 3.4 hours (interquartile range, 2.0–6.0 hr), separated into a median recognition delay (time from emergency department triage to antibiotic order) of 2.7 hours(interquartile range, 1.5–4.7 hr) and median administration delay (time from antibiotic order to infusion) of 0.6 hours (0.3–1.2 hr). Adjusting for other risk factors, both recognition delay and administration delay were associated with mortality, but pairwise comparison with a no-delay reference group was not significant for up to 6 hours of recognition delay or up to 1.5 hours of administration delay.

CONCLUSIONS: 

Both recognition delays and administration delays were associated with increased hospital mortality, but only for longer delays. These results suggest that both metrics may be important to measure and improve for patients with suspected sepsis but do not support targets less than 1 hour.

 

 

 

 

Argatroban versus heparin in patients without heparin-induced thrombocytopenia during venovenous extracorporeal membrane oxygenation: a propensity-score matched study

 

Argatroban versus heparin in patients without heparin-induced thrombocytopenia during venovenous extracorporeal membrane oxygenation: a propensity-score matched study

by Christoph Fisser, Maren Winkler, Maximilian V. Malfertheiner, Alois Philipp, Maik Foltan, Dirk Lunz, Florian Zeman, Lars S. Maier, Matthias Lubnow and Thomas Müller 

Critical Care volume 25, Article number: 160 (2021)

Background

During venovenous extracorporeal membrane oxygenation (vvECMO), direct thrombin inhibitors are considered by some potentially advantageous over unfractionated heparin (UFH). We tested the hypothesis that Argatroban is non-inferior to UFH regarding thrombosis and bleeding during vvECMO.

Methods

We conducted a propensity-score matched observational non-inferiority study of consecutive patients without heparin-induced-thrombocytopenia (HIT) on vvECMO, treated between January 2006 and March 2019 in the medical intensive care unit at the University Hospital Regensburg. Anticoagulation was realized with UFH until August 2017 and with Argatroban from September 2017 onwards. Target activated partial thromboplastin time was 50 ± 5seconds in both groups. Primary composite endpoint was major thrombosis and/or major bleeding. Major bleeding was defined as a drop in hemoglobin of ≥ 2 g/dl/day or in transfusion of ≥ 2 packed red cells/24 h, or retroperitoneal, cerebral, or pulmonary bleeding. Major thrombosis was defined as obstruction of > 50% of the vessel lumen diameter by means of duplex sonography. We also assessed technical complications such as oxygenator defects or pump head thrombosis, the time-course of platelets, and the cost of anticoagulation (including HIT-testing).

Results

Out of 465 patients receiving UFH, 78 were matched to 39 patients receiving Argatroban. The primary endpoint occurred in 79% of patients in the Argatroban group and in 83% in the UFH group (non-inferiority for Argatroban, p = 0.026). The occurrence of technical complications was equally distributed (Argatroban 49% vs. UFH 42%, p = 0.511). The number of platelets was similar in both groups before ECMO therapy but lower in the UFH group after end of ECMO support (median [IQR]: 141 [104;198]/nl vs. 107 [54;171]/nl, p = 0.010). Anticoagulation costs per day of ECMO were higher in the Argatroban group (€26 [13.8;53.0] vs. €0.9 [0.5;1.5], p < 0.001) but not after accounting for blood products and HIT-testing (€63 [42;171) vs. €40 [17;158], p = 0.074).

Conclusion

In patients without HIT on vvECMO, Argatroban was non-inferior to UFH regarding bleeding and thrombosis. The occurrence of technical complications was similarly distributed. Argatroban may have less impact on platelet decrease during ECMO, but this finding needs further evaluation. Direct drug costs were higher for Argatroban but comparable to UFH after accounting for HIT-testing and transfusions.

Circadian rhythms in septic shock patients

Circadian rhythms in septic shock patients

 

by Gunnar Lachmann, Bharath Ananthasubramaniam, Viktor A. Wünsch, Lara-Marie Scherfig, Clarissa von Haefen, Cornelia Knaak, Andreas Edel, Lukas Ehlen, Barbara Koller, Anton Goldmann, Hanspeter Herzel, Achim Kramer and Claudia Spies 

 

Annals of Intensive Care volume 11, Article number: 64 (2021) 

 

Background

Despite the intensive efforts to improve the diagnosis and therapy of sepsis over the last decade, the mortality of septic shock remains high and causes substantial socioeconomical burden of disease. The function of immune cells is time-of-day-dependent and is regulated by several circadian clock genes. This study aims to investigate whether the rhythmicity of clock gene expression is altered in patients with septic shock.

Methods

This prospective pilot study was performed at the university hospital Charité–Universitätsmedizin Berlin, Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK). We included 20 patients with septic shock between May 2014 and January 2018, from whom blood was drawn every 4 h over a 24-h period to isolate CD14-positive monocytes and to measure the expression of 17 clock and clock-associated genes. Of these patients, 3 whose samples expressed fewer than 8 clock genes were excluded from the final analysis. A rhythmicity score SP was calculated, which comprises values between -1 (arrhythmic) and 1 (rhythmic), and expression data were compared to data of a healthy study population additionally.

Results

77% of the measured clock genes showed inconclusive rhythms, i.e., neither rhythmic nor arrhythmic. The clock genes NR1D1, NR1D2 and CRY2 were the most rhythmic, while CLOCK and ARNTL were the least rhythmic. Overall, the rhythmicity scores for septic shock patients were significantly (p < 0.0001) lower (0.23 ± 0.26) compared to the control group (12 healthy young men, 0.70 ± 0.18). In addition, the expression of clock genes CRY1, NR1D1, NR1D2, DBP, and PER2 was suppressed in septic shock patients and CRY2 was significantly upregulated compared to controls.

Conclusion

Molecular rhythms in immune cells of septic shock patients were substantially altered and decreased compared to healthy young men. The decrease in rhythmicity was clock gene-dependent. The loss of rhythmicity and down-regulation of clock gene expression might be caused by sepsis and might further deteriorate immune responses and organ injury, but further studies are necessary to understand underlying pathophysiological mechanisms.

Novel criteria to classify ARDS severity using a machine learning approach

 

Novel criteria to classify ARDS severity using a machine learning approach

 

by Mohammed Sayed, David Riaño and Jesús Villar

 

Critical Care volume 25, Article number: 150 (2021)

Background

Usually, arterial oxygenation in patients with the acute respiratory distress syndrome (ARDS) improves substantially by increasing the level of positive end-expiratory pressure (PEEP). Herein, we are proposing a novel variable [PaO2/(FiO2xPEEP) or P/FPE] for PEEP ≥ 5 to address Berlin’s definition gap for ARDS severity by using machine learning (ML) approaches.

Methods

We examined P/FPE values delimiting the boundaries of mild, moderate, and severe ARDS. We applied ML to predict ARDS severity after onset over time by comparing current Berlin PaO2/FiO2 criteria with P/FPE under three different scenarios. We extracted clinical data from the first 3 ICU days after ARDS onset (N = 2738, 1519, and 1341 patients, respectively) from MIMIC-III database according to Berlin criteria for severity. Then, we used the multicenter database eICU (2014–2015) and extracted data from the first 3 ICU days after ARDS onset (N = 5153, 2981, and 2326 patients, respectively). Disease progression in each database was tracked along those 3 ICU days to assess ARDS severity. Three robust ML classification techniques were implemented using Python 3.7 (LightGBM, RF, and XGBoost) for predicting ARDS severity over time.

Results

P/FPE ratio outperformed PaO2/FiO2 ratio in all ML models for predicting ARDS severity after onset over time (MIMIC-III: AUC 0.711–0.788 and CORR 0.376–0.566; eICU: AUC 0.734–0.873 and CORR 0.511–0.745).

Conclusions

The novel P/FPE ratio to assess ARDS severity after onset over time is markedly better than current PaO2/FiO2 criteria. The use of P/FPE could help to manage ARDS patients with a more precise therapeutic regimen for each ARDS category of severity.

ABO blood types and sepsis mortality

 

ABO blood types and sepsis mortality

Theis S. Itenov, Daniel I. Sessler, Ashish K. Khanna, Sisse R. Ostrowski, Pär I. Johansson, Christian Erikstrup, Ole B. Pedersen, Sofie L. Rygård, Lars B. Holst, Morten H. Bestle, Lars Hein, Anne Lindhardt, Hami Tousi, Mads H. Andersen, Thomas Mohr, Jens D. Lundgren

Annals of Intensive Care volume 11, Article number: 61 (2021)

Background

We aimed to determine if the ABO blood types carry different risks of 30-day mortality, acute kidney injury (AKI), and endothelial damage in critically ill patients with sepsis. This was a retrospective cohort study of three independent cohorts of critically ill patients from the United States and Scandinavia consisting of adults with septic shock. We compared the 30-day mortality across the blood types within each cohort and pooled the results in a meta-analysis. We also estimated the incidence of AKI and degree of endothelial damage, as measured by blood concentrations of soluble thrombomodulin and syndecan-1.

Results

We included 12,342 patients with severe sepsis. In a pooled analysis blood type B carried a slightly lower risk of 30-day all-cause mortality compared to non-blood type B (adjusted HR 0.88; 95%-CI 0.79–0.98; p = 0.02). There was no difference in the risk of AKI. Soluble thrombomodulin and syndecan-1 concentrations were lower in patients with blood type B and O compared to blood type A, suggesting less endothelial damage.

Conclusion

Septic patients with blood type B had less endothelial damage, and a small reduction in mortality. The exposure is, however, unmodifiable.

The impact of frailty on survival in elderly intensive care patients with COVID-19: the COVIP study

 

The impact of frailty on survival in elderly intensive care patients with COVID-19: the COVIP study

by Christian Jung, Hans Flaatten, Jesper Fjølner, Raphael Romano Bruno, Bernhard Wernly, Antonio Artigas, Bernardo Bollen Pinto, Joerg C. Schefold, Georg Wolff, Malte Kelm, Michael Beil, Sigal Sviri, Peter Vernon van Heerden, Wojciech Szczeklik, Miroslaw Czuczwar, Muhammed Elhadi… 

Critical Care volume 25, Article number: 149 (2021) 

Background

The COVID-19 pandemic has led highly developed healthcare systems to the brink of collapse due to the large numbers of patients being admitted into hospitals. One of the potential prognostic indicators in patients with COVID-19 is frailty. The degree of frailty could be used to assist both the triage into intensive care, and decisions regarding treatment limitations. Our study sought to determine the interaction of frailty and age in elderly COVID-19 ICU patients.

Methods

A prospective multicentre study of COVID-19 patients ≥ 70 years admitted to intensive care in 138 ICUs from 28 countries was conducted. The primary endpoint was 30-day mortality. Frailty was assessed using the clinical frailty scale. Additionally, comorbidities, management strategies and treatment limitations were recorded.

Results

The study included 1346 patients (28% female) with a median age of 75 years (IQR 72–78, range 70–96), 16.3% were older than 80 years, and 21% of the patients were frail. The overall survival at 30 days was 59% (95% CI 56–62), with 66% (63–69) in fit, 53% (47–61) in vulnerable and 41% (35–47) in frail patients (p < 0.001). In frail patients, there was no difference in 30-day survival between different age categories. Frailty was linked to an increased use of treatment limitations and less use of mechanical ventilation. In a model controlling for age, disease severity, sex, treatment limitations and comorbidities, frailty was independently associated with lower survival.

Conclusion

Frailty provides relevant prognostic information in elderly COVID-19 patients in addition to age and comorbidities.

Corticosteroids in COVID-19 and non-COVID-19 ARDS: a systematic review and meta-analysis

 

Corticosteroids in COVID-19 and non-COVID-19 ARDS: a systematic review and meta-analysis

Intensive Care Medicine Published: 19 April 2021

Purpose

Corticosteroids are now recommended for patients with severe COVID-19 including those with COVID-related ARDS. This has generated renewed interest regarding whether corticosteroids should be used in non-COVID ARDS as well. The objective of this study was to summarize all RCTs examining the use of corticosteroids in ARDS.

Methods

The protocol of this study was pre-registered on PROSPERO (CRD42020200659). We searched online databases including MEDLINE, EMBASE, CDC library of COVID research, CINAHL, and COCHRANE. We included RCTs that compared the effect of corticosteroids to placebo or usual care in adult patients with ARDS, including patients with COVID-19. Three reviewers abstracted data independently and in duplicate using a pre-specified standardized form. We assessed individual study risk of bias using the revised Cochrane ROB-2 tool and rated certainty in outcomes using GRADE methodology. We pooled data using a random effects model. The main outcome for this review was 28-day-mortality.

Results

We included 18 RCTs enrolling 2826 patients. The use of corticosteroids probably reduced mortality in patients with ARDS of any etiology (2740 patients in 16 trials, RR 0.82, 95% CI 0.72–0.95, ARR 8.0%, 95% CI 2.2–12.5%, moderate certainty). Patients who received a longer course of corticosteroids (over 7 days) had higher rates of survival compared to a shorter course.

Conclusion

The use of corticosteroids probably reduces mortality in patients with ARDS. This effect was consistent between patients with COVID-19 and non-COVID-19 ARDS, corticosteroid types, and dosage.