9 research outputs found
Pressure ulcers in patients with COVID-19 acute respiratory distress syndrome undergoing prone positioning in the intensive care unit: a pre- and post-intervention study
Background: Prone positioning has been widely used to improve oxygenation and reduce ventilator-induced lung injury in patients with severe COVID-19 acute respiratory distress syndrome (ARDS). One major complication associated with prone positioning is the development of pressure ulcers (PUs).
Aim: This study aimed to determine the impact of a prevention care bundle on the incidence of PUs in patients with COVID-19 ARDS undergoing prone positioning in the intensive care unit.
Study design: This was a single-centre pre and post-test intervention study which adheres to the Standards for Reporting Implementation Studies (StaRI) guidelines. The intervention included a care bundle addressing the following: increasing frequency of head turns, use of an open gel head ring, application of prophylactic dressings to bony prominences, use of a pressure redistribution air mattress, education of staff in the early identification of evolving PUs through regular and rigorous skin inspection and engaging in bedside training sessions with nursing and medical staff. The primary outcome of interest was the incidence of PU development. The secondary outcomes of interest were severity of PU development and the anatomical location of the PUs.
Results: In the pre-intervention study, 20 patients were included and 80% (n = 16) of these patients developed PUs, comprising 34 ulcers in total. In the post-intervention study, a further 20 patients were included and 60% (n = 12) of these patients developed PUs, comprising 32 ulcers in total. This marks a 25% reduction in the number of patients developing a PU, and a 6% decrease in the total number of PUs observed. Grade II PUs were the most prevalent in both study groups (65%, n = 22; 88%, n = 28, respectively). In the post-intervention study, there was a reduction in the incidence of grade III and deep tissue injuries (pre-intervention 6%, n = 2 grade III, 6% n = 2 deep tissue injuries; post-intervention no grade III ulcers, grade IV ulcers, or deep tissues injuries were recorded). However, there was an increase in the number of unstageable PUs in the post-intervention group with 6% (n = 2) of PUs being classified as unstageable, meanwhile there were no unstageable PUs in the pre-intervention group. This is an important finding to consider as unstageable PUs can indicate deep tissue damage and therefore need to be considered alongside PUs of a more severe grade (grade III, grade IV, and deep tissue injuries).
Conclusion: The use of a new evidence-based care bundle for the prevention of PUs in the management of patients in the prone position has the potential to reduce the incidence of PU development. Although improvements were observed following alterations to standard practice, further research is needed to validate these findings.
Relevance to clinical practice: The use of a new, evidence-based care bundle in the management of patients in the prone position has the potential to reduce the incidence of PUs.</p
Corrigendum to 'A linear prognostic score based on the ratio of interleukin-6 to interleukin-10 predicts outcomes in COVID-19'
The authors wish to correct a typographical error in the
manuscript. In both the abstract and Section 3.4 of the original manuscript, a
1-point increase in the Dublin-Boston score was described as being associated
with a 5.6 times increased odds (OR 5.62, 95% CI = 3.229.81, P = 1.2 ÂŁ 109 )
for a more severe outcome. While the OR and P-value stated are correct, the CI
should instead have read “3.229.81”. The CI listed in Table 3 of the original
manuscript, which accompanied Section 3.4, is correct. The authors regret any
confusion caused, and appreciate the opportunity to correct this mistake.</div
A linear prognostic score based on the ratio of interleukin-6 to interleukin-10 predicts outcomes in COVID-19
Background: Prognostic tools are required to guide clinical decision-making in COVID-19.Methods: We studied the relationship between the ratio of interleukin (IL)-6 to IL-10 and clinical outcome in 80 patients hospitalized for COVID-19, and created a simple 5-point linear score predictor of clinical outcome, the Dublin-Boston score. Clinical outcome was analysed as a three-level ordinal variable ("Improved", "Unchanged", or "Declined"). For both IL-6:IL-10 ratio and IL-6 alone, we associated clinical outcome with a) baseline biomarker levels, b) change in biomarker level from day 0 to day 2, c) change in biomarker from day 0 to day 4, and d) slope of biomarker change throughout the study. The associations between ordinal clinical outcome and each of the different predictors were performed with proportional odds logistic regression. Associations were run both "unadjusted" and adjusted for age and sex. Nested cross-validation was used to identify the model for incorporation into the Dublin-Boston score.Findings: The 4-day change in IL-6:IL-10 ratio was chosen to derive the Dublin-Boston score. Each 1 point increase in the score was associated with a 5.6 times increased odds for a more severe outcome (OR 5.62, 95% CI -3.22-9.81, P = 1.2 Ă— 10-9). Both the Dublin-Boston score and the 4-day change in IL-6:IL-10 significantly outperformed IL-6 alone in predicting clinical outcome at day 7.Interpretation: The Dublin-Boston score is easily calculated and can be applied to a spectrum of hospitalized COVID-19 patients. More informed prognosis could help determine when to escalate care, institute or remove mechanical ventilation, or drive considerations for therapies.</p
Use of a novel “Split” ventilation system in bench and porcine modeling of acute respiratory distress syndrome
Split ventilation (using a single ventilator to ventilate multiple patients) is technically feasible. However, connecting two patients with acute respiratory distress syndrome (ARDS) and differing lung mechanics to a single ventilator is concerning. This study aimed to: (1) determine functionality of a split ventilation system in benchtop tests, (2) determine whether standard ventilation would be superior to split ventilation in a porcine model of ARDS and (3) assess usability of a split ventilation system with minimal specific training. The functionality of a split ventilation system was assessed using test lungs. The usability of the system was assessed in simulated clinical scenarios. The feasibility of the system to provide modified lung protective ventilation was assessed in a porcine model of ARDS (n = 30). In bench testing a split ventilation system independently ventilated two test lungs under conditions of varying compliance and resistance. In usability tests, a high proportion of naïve operators could assemble and use the system. In the porcine model, modified lung protective ventilation was feasible with split ventilation and produced similar respiratory mechanics, gas exchange and biomarkers of lung injury when compared to standard ventilation. Split ventilation can provide some elements of lung protective ventilation and is feasible in bench testing and an in vivo model of ARDS
Prone positioning improves oxygenation and lung recruitment in patients with SARS-CoV-2 acute respiratory distress syndrome; a single centre cohort study of 20 consecutive patients
Objective: We aimed to characterize the effects of prone positioning on respiratory mechanics and oxygenation in invasively ventilated patients with SARS-CoV-2 ARDS.Results: This was a prospective cohort study in the Intensive Care Unit (ICU) of a tertiary referral centre. We included 20 consecutive, invasively ventilated patients with laboratory confirmed SARS-CoV-2 related ARDS who underwent prone positioning in ICU as part of their management. The main outcome was the effect of prone positioning on gas exchange and respiratory mechanics. There was a median improvement in the PaO2/FiO2 ratio of 132 in the prone position compared to the supine position (IQR 67-228). We observed lower PaO2/FiO2 ratios in those with low ( median) static compliance (P < 0.05). There was no significant difference in respiratory system static compliance with prone positioning. Prone positioning was effective in improving oxygenation in SARS-CoV-2 ARDS. Furthermore, poor respiratory system static compliance was common and was associated with disease severity. Improvements in oxygenation were partly due to lung recruitment. Prone positioning should be considered in patients with SARS-CoV-2 ARDS.</p
A randomised, double-blind, placebo-controlled, pilot trial of intravenous plasma purified alpha-1 antitrypsin for SARS-CoV-2-induced Acute Respiratory Distress Syndrome: a structured summary of a study protocol for a randomised, controlled trial
Objectives: The primary objective is to
demonstrate that, in patients with PCR-confirmed SARS-CoV-2 resulting in Acute
Respiratory Distress Syndrome (ARDS), administration of 120mg/kg of body weight
of intravenous Prolastin®(plasma-purified alpha-1 antitrypsin) reduces
circulating plasma levels of interleukin-6 (IL-6). Secondary objectives are to
determine the effects of intravenous Prolastin® on important clinical outcomes
including the incidence of adverse events (AEs) and serious adverse events
(SAEs).
Trial design: Phase
2, randomised, double-blind, placebo-controlled, pilot trial.
Participants: The
study will be conducted in Intensive Care Units in hospitals across Ireland.
Patients with a laboratory-confirmed diagnosis of SARS-CoV-2-infection,
moderate to severe ARDS (meeting Berlin criteria for a diagnosis of ARDS with a
PaO2/FiO2 ratio 18 years
of age and requiring invasive or non-invasive mechanical ventilation. All
individuals meeting any of the following exclusion criteria at baseline or
during screening will be excluded from study participation: more than 96 hours
has elapsed from onset of ARDS; age < 18 years; known to be pregnant or
breastfeeding; participation in a clinical trial of an investigational
medicinal product (other than antibiotics or antivirals) within 30 days; major
trauma in the prior 5 days; presence of any active malignancy (other than
nonmelanoma skin cancer) which required treatment within the last year; WHO
Class III or IV pulmonary hypertension; pulmonary embolism prior to hospital
admission within past 3 months; currently receiving extracorporeal life support
(ECLS); chronic kidney disease receiving dialysis; severe chronic liver disease
with Child-Pugh score > 12; DNAR (Do Not Attempt Resuscitation) order in
place; treatment withdrawal imminent within 24 hours; Prisoners; non-English
speaking patients or those who do not adequately understand verbal or written
information unless an interpreter is available; IgA deficiency.
Intervention and
comparator: Intervention: Either a once weekly intravenous
infusion of Prolastin® at 120mg/kg of body weight for 4 weeks or a single dose
of Prolastin® at 120mg/kg of body weight intravenously followed by once weekly
intravenous infusion of an equal volume of 0.9% sodium chloride for a further 3
weeks. Comparator (placebo): An equal volume of 0.9% sodium chloride
intravenously once per week for four weeks.
Main outcomes: The
primary effectiveness outcome measure is the change in plasma concentration of
IL-6 at 7 days as measured by ELISA. Secondary outcomes include: safety and
tolerability of Prolastin® in the respective groups (as defined by the number
of SAEs and AEs); PaO2/FiO2 ratio;
respiratory compliance; sequential organ failure assessment (SOFA) score;
mortality; time on ventilator in days; plasma concentration of alpha-1
antitrypsin (AAT) as measured by nephelometry; plasma concentrations of
interleukin-1β (IL-1β), interleukin-8 (IL-8), interleukin-10 (IL-10), soluble
TNF receptor 1 (sTNFR1, a surrogate marker for TNF-α) as measured by ELISA;
development of shock; acute kidney injury; need for renal replacement therapy;
clinical relapse, as defined by the need for readmission to the ICU or a marked
decline in PaO2/FiO2 or
development of shock or mortality following a period of sustained clinical
improvement; secondary bacterial pneumonia as defined by the combination of
radiographic findings and sputum/airway secretion microscopy and culture.
Randomisation: Following
informed consent/assent patients will be randomised. The randomisation lists
will be prepared by the study statistician and given to the unblinded trial
personnel. However, the statistician will not be exposed to how the planned
treatment will be allocated to the treatment codes. Randomisation will be
conducted in a 1:1:1 ratio, stratified by site and age.
Blinding (masking): The
investigator, treating physician, other members of the site research team and
patients will be blinded to treatment allocation. The clinical trial pharmacy
personnel and research nurses will be unblinded to facilitate intervention and
placebo preparation. The unblinded individuals will keep the treatment
information confidential. The infusion bag will be masked at the time of
preparation and will be administered via a masked infusion set to maintain blinding.
Numbers to be randomised (sample
size): A total of 36 patients will be recruited and
randomised in a 1:1:1 ratio to each of the trial arms.
</p
Von Willebrand factor propeptide in severe coronavirus disease 2019 (COVID-19): evidence of acute and sustained endothelial cell activation
Endothelial cell (EC) activation plays a key role in the pathogenesis of pulmonary microvascular occlusion, which is a hallmark of severe coronavirus disease 2019 (COVID-19). Consistent with EC activation, increased plasma von Willebrand factor antigen (VWF:Ag) levels have been reported in COVID-19. Importantly however, studies in other microangiopathies have shown that plasma VWF propeptide (VWFpp) is a more sensitive and specific measure of acute EC activation. In the present study, we further investigated the nature of EC activation in severe COVID-19. Markedly increased plasma VWF:Ag [median (interquatile range, IQR) 608·8 (531–830)iu/dl] and pro-coagulant factor VIII (FVIII) levels [median (IQR) 261·9 (170–315) iu/dl] were seen in patients with severe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Sequential testing showed that these elevated VWF–FVIII complex levels remained high for up to 3 weeks. Similarly, plasma VWFpp levels were also markedly elevated [median (IQR) 324·6 (267–524) iu/dl]. Interestingly however, the VWFpp/VWF:Ag ratio was reduced, demonstrating that decreased VWF clearance contributes to the elevated plasma VWF:Ag levels in severe COVID-19. Importantly, plasma VWFpp levels also correlated with clinical severity indices including the Sequential Organ Failure Assessment (SOFA) score, Sepsis-Induced Coagulopathy (SIC) score and the ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F ratio). Collectively, these findings support the hypothesis that sustained fulminant EC activation is occurring in severe COVID-19, and further suggest that VWFpp may have a role as a biomarker in this setting
A randomized, double-blind, placebo-controlled trial of intravenous alpha-1 antitrypsin for ARDS secondary to COVID-19
Background: Patients with severe coronavirus disease 2019 (COVID-19) develop a febrile pro-inflammatory cytokinemia with accelerated progression to acute respiratory distress syndrome (ARDS). Here we report the results of a phase 2, multicenter, randomized, double-blind, placebo-controlled trial of intravenous (IV) plasma-purified alpha-1 antitrypsin (AAT) for moderate to severe ARDS secondary to COVID-19 (EudraCT 2020-001391-15).Â
Methods: Patients (n = 36) were randomized to receive weekly placebo, weekly AAT (Prolastin, Grifols, S.A.; 120 mg/kg), or AAT once followed by weekly placebo. The primary endpoint was the change in plasma interleukin (IL)-6 concentration at 1 week. In addition to assessing safety and tolerability, changes in plasma levels of IL-1β, IL-8, IL-10, and soluble tumor necrosis factor receptor 1 (sTNFR1) and clinical outcomes were assessed as secondary endpoints.Â
Findings: Treatment with IV AAT resulted in decreased inflammation and was safe and well tolerated. The study met its primary endpoint, with decreased circulating IL-6 concentrations at 1 week in the treatment group. This was in contrast to the placebo group, where IL-6 was increased. Similarly, plasma sTNFR1 was substantially decreased in the treatment group while remaining unchanged in patients receiving placebo. IV AAT did not definitively reduce levels of IL-1β, IL-8, and IL-10. No difference in mortality or ventilator-free days was observed between groups, although a trend toward decreased time on ventilator was observed in AAT-treated patients.Â
Conclusions: In patients with COVID-19 and moderate to severe ARDS, treatment with IV AAT was safe, feasible, and biochemically efficacious. The data support progression to a phase 3 trial and prompt further investigation of AAT as an anti-inflammatory therapeutic.Â
Funding: ECSA-2020-009; Elaine Galwey Research Bursary.</p
Characterization of the inflammatory response to severe COVID-19 illness.
Rationale: Coronavirus disease (COVID-19) is a global
threat to health. Its inflammatory characteristics are incompletely understood. Objectives: To define the cytokine profile of COVID-19
and to identify evidence of immunometabolic alterations in those with severe
illness. Methods: Levels of IL-1β, IL-6, IL-8, IL-10, and
sTNFR1 (soluble tumor necrosis factor receptor 1) were assessed in plasma from
healthy volunteers, hospitalized but stable patients with COVID-19 (COVIDstable patients), patients with COVID-19 requiring
ICU admission (COVIDICU patients), and patients with severe
community-acquired pneumonia requiring ICU support (CAPICU patients). Immunometabolic markers were
measured in circulating neutrophils from patients with severe COVID-19. The
acute phase response of AAT (alpha-1 antitrypsin) to COVID-19 was also
evaluated. Measurements and Main
Results: IL-1β, IL-6, IL-8, and sTNFR1 were all
increased in patients with COVID-19. COVIDICU patients could be clearly differentiated
from COVIDstable patients, and demonstrated higher levels of
IL-1β, IL-6, and sTNFR1 but lower IL-10 than CAPICU patients. COVID-19 neutrophils displayed
altered immunometabolism, with increased cytosolic PKM2 (pyruvate kinase M2),
phosphorylated PKM2, HIF-1α (hypoxia-inducible factor-1α), and lactate. The production
and sialylation of AAT increased in COVID-19, but this antiinflammatory
response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly
higher in patients requiring ICU admission (P < 0.0001). In critically unwell patients
with COVID-19, increases in IL-6:AAT predicted prolonged ICU stay and
mortality, whereas improvement in IL-6:AAT was associated with clinical
resolution (P
Conclusions: The COVID-19 cytokinemia is distinct from
that of other types of pneumonia, leading to organ failure and ICU need.
Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness.
Cytokine ratios may predict outcomes in this population.
Measurements and Main Results: IL-1β, IL-6, IL-8, and sTNFR1 were all increased in
patients with COVID-19. COVIDICU patients could be clearly differentiated
from COVIDstable patients, and demonstrated higher levels of
IL-1β, IL-6, and sTNFR1 but lower IL-10 than CAPICU patients. COVID-19 neutrophils displayed
altered immunometabolism, with increased cytosolic PKM2 (pyruvate kinase M2),
phosphorylated PKM2, HIF-1α (hypoxia-inducible factor-1α), and lactate. The production
and sialylation of AAT increased in COVID-19, but this antiinflammatory
response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly
higher in patients requiring ICU admission (P < 0.0001). In critically unwell patients
with COVID-19, increases in IL-6:AAT predicted prolonged ICU stay and
mortality, whereas improvement in IL-6:AAT was associated with clinical
resolution (P
Conclusions: The COVID-19 cytokinemia is distinct from
that of other types of pneumonia, leading to organ failure and ICU need.
Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness.
Cytokine ratios may predict outcomes in this population.</p