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1.
Crit Care Explor ; 6(5): e1094, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38727717

ABSTRACT

OBJECTIVES: Near-infrared spectroscopy (NIRS) is a potentially valuable modality to monitor the adequacy of oxygen delivery to the brain and other tissues in critically ill patients, but little is known about the physiologic determinants of NIRS-derived tissue oxygen saturations. The purpose of this study was to assess the contribution of routinely measured physiologic parameters to tissue oxygen saturation measured by NIRS. DESIGN: An observational sub-study of patients enrolled in the Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) randomized feasibility trial. SETTING: Two ICUs in the United Kingdom. PATIENTS: Patients were recruited for the RADAR-2 study, which compared a conservative approach to fluid therapy and deresuscitation with usual care. Those included in this sub-study underwent continuous NIRS monitoring of cerebral oxygen saturations (SctO2) and quadriceps muscle tissue saturations (SmtO2). INTERVENTION: Synchronized and continuous mean arterial pressure (MAP), heart rate (HR), and pulse oximetry (oxygen saturation, Spo2) measurements were recorded alongside NIRS data. Arterial Paco2, Pao2, and hemoglobin concentration were recorded 12 hourly. Linear mixed effect models were used to investigate the association between these physiologic variables and cerebral and muscle tissue oxygen saturations. MEASUREMENTS AND MAIN RESULTS: Sixty-six patients were included in the analysis. Linear mixed models demonstrated that Paco2, Spo2, MAP, and HR were weakly associated with SctO2 but only explained 7.1% of the total variation. Spo2 and MAP were associated with SmtO2, but together only explained 0.8% of its total variation. The remaining variability was predominantly accounted for by between-subject differences. CONCLUSIONS: Our findings demonstrated that only a small proportion of variability in NIRS-derived cerebral and tissue oximetry measurements could be explained by routinely measured physiologic variables. We conclude that for NIRS to be a useful monitoring modality in critical care, considerable further research is required to understand physiologic determinants and prognostic significance.


Subject(s)
Critical Illness , Oximetry , Oxygen Saturation , Spectroscopy, Near-Infrared , Humans , Spectroscopy, Near-Infrared/methods , Male , Female , Oxygen Saturation/physiology , Middle Aged , Aged , Oximetry/methods , Monitoring, Physiologic/methods , Brain/metabolism , Brain/blood supply , United Kingdom , Oxygen/metabolism , Oxygen/blood , Oxygen/analysis , Intensive Care Units , Quadriceps Muscle/metabolism , Quadriceps Muscle/blood supply
2.
Aust Crit Care ; 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38627116

ABSTRACT

OBJECTIVES: The aim of this study was to synthesise the evidence concerning communication in critically ill tracheostomy patients dependent on cuff inflation. The aim was to identify the psychological impact on patients awake and alert with tracheostomies but unable to speak; strategies utilised to enable communication and facilitators and barriers for the success of these strategies. REVIEW METHOD USED: This scoping review was conducted using the Joanna Briggs Institute framework and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. DATA SOURCES: CINAHL, Embase, Medline, and Web of Science were searched from 1st January 2000 to 30th September 2023 and supplemented with hand searching of references from included studies. REVIEW METHODS: Studies were eligible if they addressed the psychological impact of voicelessness and/or the structure, process, and outcomes of augmentative and alternative communication (AAC) systems, in addition to facilitators and barriers to effectiveness. The population of interest included critically ill tracheostomy patients dependent on cuff inflation, their families, and healthcare workers. Screening and data extraction were undertaken by two reviewers independently. Data analysis involved descriptive statistics and content analysis. RESULTS: A total of 23 studies met the inclusion criteria: 11 were qualitative, nine were quantitative, and three were mixed-methods studies. Voicelessness elicited negative emotions, predominantly frustration. AAC systems, encompassing unaided and aided (low-tech and high-tech) methods, presented both advantages and drawbacks. High-tech strategies held promise for patients with physical limitations. Patients equally appreciated the support offered through unaided strategies, including eye contact and touch. Facilitating factors included speech therapy involvement and assessment. Patient-related challenges were the most frequent barriers. CONCLUSION: Facilitating meaningful communication for critically ill tracheostomy patients dependent on cuff inflation is of paramount psychological significance. Whilst AAC systems are practicable, they are not without limitations, implying the absence of a universally applicable solution. This underscores the importance of continuous evaluation, reinforced by a multidisciplinary team. REVIEW PROTOCOL REGISTERED: 27 July 2022. REVIEW REGISTRATION: Open Science Framework Registries: https://osf.io/kbrjn/.

3.
Respir Res ; 25(1): 188, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38678280

ABSTRACT

Repetitive bouts of coughing expose the large airways to significant cycles of shear stress. This leads to the release of alarmins and the tussive agent adenosine triphosphate (ATP) which may be modulated by the activity of ion channels present in the human airway. This study aimed to investigate the role of the transient receptor potential subfamily vanilloid member 2 (TRPV2) channel in mechanically induced ATP release from primary bronchial epithelial cells (PBECs).PBECs were obtained from individuals undergoing bronchoscopy. They were cultured in vitro and exposed to mechanical stress in the form of compressive and fluid shear stress (CFSS) or fluid shear stress (FSS) alone at various intensities. ATP release was measured using a luciferin-luciferase assay. Functional TRPV2 protein expression in human PBECs was investigated by confocal calcium imaging. The role of TRPV2 inhibition on FSS-induced ATP release was investigated using the TRPV2 inhibitor tranilast or siRNA knockdown of TRPV2. TRPV2 protein expression in human lung tissue was also determined by immunohistochemistry.ATP release was significantly increased in PBECs subjected to CFSS compared with control (unstimulated) PBECs (N = 3, ***P < 0.001). PBECs expressed functional TRPV2 channels. TRPV2 protein was also detected in fixed human lung tissue. ATP release from FFS stimulated PBECs was decreased by the TRPV2 inhibitor tranilast (N = 3, **P < 0.01) (vehicle: 159 ± 17.49 nM, tranilast: 25.08 ± 5.1 nM) or by TRPV2 siRNA knockdown (N = 3, *P < 0.05) (vehicle: 197 ± 24.52 nM, siRNA: 119 ± 26.85 nM).In conclusion, TRPV2 is expressed in the human airway and modulates ATP release from mechanically stimulated PBECs.


Subject(s)
Adenosine Triphosphate , Bronchi , Epithelial Cells , TRPV Cation Channels , Humans , TRPV Cation Channels/metabolism , TRPV Cation Channels/genetics , Adenosine Triphosphate/metabolism , Bronchi/metabolism , Cells, Cultured , Epithelial Cells/metabolism , Stress, Mechanical , Male , Mechanotransduction, Cellular/physiology
4.
Crit Care ; 28(1): 97, 2024 03 23.
Article in English | MEDLINE | ID: mdl-38521954

ABSTRACT

Sepsis is a life-threatening condition characterised by endothelial barrier dysfunction and impairment of normal microcirculatory function, resulting in a state of hypoperfusion and tissue oedema. No specific pharmacological therapies are currently used to attenuate microvascular injury. Given the prominent role of endothelial breakdown and microcirculatory dysfunction in sepsis, there is a need for effective strategies to protect the endothelium. In this review we will discuss key mechanisms and putative therapeutic agents relevant to endothelial barrier function.


Subject(s)
Sepsis , Humans , Microcirculation , Sepsis/drug therapy , Endothelium , Endothelium, Vascular/metabolism
5.
Crit Care Explor ; 6(4): e1069, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38545606

ABSTRACT

OBJECTIVES: To evaluate the current management of new-onset atrial fibrillation and compare differences in practice regionally. DESIGN: Cross-sectional survey. SETTING: United States, Canada, United Kingdom, Europe, Australia, and New Zealand. SUBJECTS: Critical care attending physicians/consultants and fellows. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 386 surveys were included in our analysis. Rate control was the preferred treatment approach for hemodynamically stable patients (69.1%), and amiodarone was the most used antiarrhythmic medication (70.9%). For hemodynamically unstable patients, a strategy of electrolyte supplementation and antiarrhythmic therapy was most common (54.7%). Physicians responding to the survey distributed by the Society of Critical Care Medicine were more likely to prescribe beta-blockers as a first-line antiarrhythmic medication (38.4%), use more transthoracic echocardiography than respondents from other regions (82.4%), and more likely to refer patients who survive their ICU stay for cardiology follow-up if they had new-onset atrial fibrillation (57.2%). The majority of survey respondents (83.0%) were interested in participating in future studies of atrial fibrillation in critically ill patients. CONCLUSIONS: Significant variation exists in the management of new-onset atrial fibrillation in critically ill patients, as well as geographic variation. Further research is necessary to inform guidelines in this population and establish if differences in practice impact long-term outcomes.

6.
Am J Respir Crit Care Med ; 209(7): 789-797, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38324017

ABSTRACT

There is considerable interest in the potential for cell-based therapies, particularly mesenchymal stromal cells (MSCs) and their products, as a therapy for acute respiratory distress syndrome (ARDS). MSCs exert effects via diverse mechanisms including reducing excessive inflammation by modulating neutrophil, macrophage and T-cell function, decreasing pulmonary permeability and lung edema, and promoting tissue repair. Clinical studies indicate that MSCs are safe and well tolerated, with promising therapeutic benefits in specific clinical settings, leading to regulatory approvals of MSCs for specific indications in some countries.This perspective reassesses the therapeutic potential of MSC-based therapies for ARDS given insights from recent cell therapy trials in both COVID-19 and in 'classic' ARDS, and discusses studies in graft-vs.-host disease, one of the few licensed indications for MSC therapies. We identify important unknowns in the current literature, address challenges to clinical translation, and propose an approach to facilitate assessment of the therapeutic promise of MSC-based therapies for ARDS.


Subject(s)
Acute Lung Injury , COVID-19 , Mesenchymal Stem Cell Transplantation , Respiratory Distress Syndrome , Humans , Lung , Acute Lung Injury/etiology , Cell- and Tissue-Based Therapy
8.
Int J Clin Pharm ; 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38332207

ABSTRACT

BACKGROUND: Thiamine di-phosphate is an essential cofactor in glucose metabolism, glutamate transformation and acetylcholinesterase activity, pathways associated with delirium occurrence. We hypothesised that a deficiency in whole blood thiamine and intravenous thiamine supplementation could impact delirium occurrence. AIM: To establish whether a deficiency in whole blood thiamine and/or intravenous thiamine supplementation within 72 h of intensive care admission is associated with delirium occurrence. METHOD: The first dataset was secondary analysis of a previous study in an intensive care unit in the Netherlands, reported in 2017. The second dataset contained consecutive intensive care admissions 2 years before (period 1: October 2014 to October 2016) and after (period 2: April 2017 to April 2019) routine thiamine supplementation was introduced within 72 h of admission. Delirium was defined as a positive Confusion Assessment Method-Intensive Care Unit score(s) in 24 h. RESULTS: Analysis of the first dataset (n = 57) using logistic regression showed no relationship between delirium and sepsis or whole blood thiamine, but a significant association with age (p = 0.014). In the second dataset (n = 3074), 15.1% received IV thiamine in period 1 and 62.6% during period 2. Hierarchical regression analysis reported reduction in delirium occurrence in the second period; this did not reach statistical significance, OR = 0.81 (95% CI 0.652-1.002); p = 0.052. CONCLUSION: No relationship was detected between whole blood thiamine and delirium occurrence on admission, at 24 and 48 h. It remains unclear whether routine intravenous thiamine supplementation during intensive care admission impacts delirium occurrence. Further prospective randomised clinical trials are needed.

9.
Crit Care Explor ; 6(1): e1028, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38213419

ABSTRACT

OBJECTIVES: Lower tidal volume ventilation (targeting 3 mL/kg predicted body weight, PBW) facilitated by extracorporeal carbon dioxide removal (ECCO2R) has been investigated as a potential therapy for acute hypoxemic respiratory failure (AHRF) in the pRotective vEntilation with veno-venouS lung assisT in respiratory failure (REST) trial. We investigated the effect of this strategy on cardiac function, and in particular the right ventricle. DESIGN: Substudy of the REST trial. SETTING: Nine U.K. ICUs. PATIENTS: Patients with AHRF (Pao2/Fio2 < 150 mm Hg [20 kPa]). INTERVENTION: Transthoracic echocardiography and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements were collected at baseline and postrandomization in patients randomized to ECCO2R or usual care. MEASUREMENTS: The primary outcome measures were a difference in tricuspid annular plane systolic excursion (TAPSE) on postrandomization echocardiogram and difference in NT-proBNP postrandomization. RESULTS: There were 21 patients included in the echocardiography cohort (ECCO2R, n = 13; usual care, n = 8). Patient characteristics were similar in both groups at baseline. Median (interquartile range) tidal volumes were lower in the ECCO2R group compared with the usual care group postrandomization; 3.6 (3.1-4.2) mL/kg PBW versus 5.2 (4.9-5.7) mL/kg PBW, respectively (p = 0.01). There was no difference in the primary outcome measure of mean (sd) TAPSE in the ECCO2R and usual care groups postrandomization; 21.3 (5.4) mm versus 20.1 (3.2) mm, respectively (p = 0.60). There were 75 patients included in the NT-proBNP cohort (ECCO2R, n = 36; usual care, n = 39). Patient characteristics were similar in both groups at baseline. Median (interquartile range [IQR]) tidal volumes were lower in the ECCO2R group than the usual care group postrandomization; 3.8 (3.3-4.2) mL/kg PBW versus 6.7 (5.8-8.1) mL/kg PBW, respectively (p < 0.0001). There was no difference in median (IQR) NT-proBNP postrandomization; 1121 (241-5370) pg/mL versus 1393 (723-4332) pg/mL in the ECCO2R and usual care groups, respectively (p = 0.30). CONCLUSIONS: In patients with AHRF, a reduction in tidal volume facilitated by ECCO2R, did not modify cardiac function.

10.
Alzheimers Dement ; 20(1): 183-194, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37522255

ABSTRACT

BACKGROUND: Delirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long-term outcomes. Recording and analyzing all delirium equally could be hindering the field's understanding of pathophysiology and identification of targeted treatments. Current delirium subtyping methods reflect clinically evident features but likely do not account for underlying biology. METHODS: The Delirium Subtyping Initiative (DSI) held three sessions with an international panel of 25 experts. RESULTS: Meeting participants suggest further characterization of delirium features to complement the existing Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision diagnostic criteria. These should span the range of delirium-spectrum syndromes and be measured consistently across studies. Clinical features should be recorded in conjunction with biospecimen collection, where feasible, in a standardized way, to determine temporal associations of biology coincident with clinical fluctuations. DISCUSSION: The DSI made recommendations spanning the breadth of delirium research including clinical features, study planning, data collection, and data analysis for characterization of candidate delirium subtypes. HIGHLIGHTS: Delirium features must be clearly defined, standardized, and operationalized. Large datasets incorporating both clinical and biomarker variables should be analyzed together. Delirium screening should incorporate communication and reasoning.


Subject(s)
Delirium , Humans , Delirium/diagnosis , Delirium/etiology , Research Design , Data Collection , Diagnostic and Statistical Manual of Mental Disorders
12.
Intensive Care Med ; 49(11): 1305-1316, 2023 11.
Article in English | MEDLINE | ID: mdl-37815560

ABSTRACT

BACKGROUND: There is controversy regarding the optimal renal-replacement therapy (RRT) modality for critically ill patients with acute kidney injury (AKI). METHODS: We conducted a secondary analysis of the STandard versus Accelerated Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial to compare outcomes among patients who initiated RRT with either continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD). We generated a propensity score for the likelihood of receiving CRRT and used inverse probability of treatment with overlap-weighting to address baseline inter-group differences. The primary outcome was a composite of death or RRT dependence at 90-days after randomization. RESULTS: We identified 1590 trial participants who initially received CRRT and 606 who initially received IHD. The composite outcome of death or RRT dependence at 90-days occurred in 823 (51.8%) patients who commenced CRRT and 329 (54.3%) patients who commenced IHD (unadjusted odds ratio (OR) 0.90; 95% confidence interval (CI) 0.75-1.09). After balancing baseline characteristics with overlap weighting, initial receipt of CRRT was associated with a lower risk of death or RRT dependence at 90-days compared with initial receipt of IHD (OR 0.81; 95% CI 0.66-0.99). This association was predominantly driven by a lower risk of RRT dependence at 90-days (OR 0.61; 95% CI 0.39-0.94). CONCLUSIONS: In critically ill patients with severe AKI, initiation of CRRT, as compared to IHD, was associated with a significant reduction in the composite outcome of death or RRT dependence at 90-days.


Subject(s)
Acute Kidney Injury , Continuous Renal Replacement Therapy , Humans , Acute Kidney Injury/therapy , Critical Illness/therapy , Renal Dialysis , Renal Replacement Therapy
13.
Crit Care Med ; 51(12): e269-e274, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37695136

ABSTRACT

OBJECTIVES: Interleukin-18 (IL-18) plasma level and latent class analysis (LCA) have separately been shown to predict prognosis and treatment response in acute respiratory distress syndrome (ARDS). IL-18 is a measure of inflammasome activation, a pathway potentially distinct from inflammation captured by biomarkers defining previously published LCA classes. We hypothesized that elevated IL-18 would identify distinct "high-risk" patients not captured by prior LCA classifications. DESIGN: Statins for acutely injured lungs from sepsis (SAILS) and hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction trial (HARP-2) are two large randomized, controlled trials in ARDS in which both LCA assignments and IL-18 levels were shown to predict mortality. We first evaluated the overlap between high IL-18 levels (≥ 800 pg/mL) with prior LCA class assignments using McNemar's test and then tested the correlation between IL-18 and LCA biomarkers using Pearson's exact test on log-2 transformed values. Our primary analysis was the association of IL-18 level with 60-day mortality in the hypoinflammatory LCA class, which was assessed using the Fisher exact test and Cox proportional hazards modeling adjusting for age, Acute Physiology and Chronic Health Evaluation score, and gender. Secondary analyses included the association of IL-18 and LCA with mortality within each IL-18/LCA subgroup. SETTING: Secondary analysis of two multicenter, randomized controlled clinical trials of ARDS patients. SUBJECTS: Six hundred eighty-three patients in SAILS and 511 patients in HARP-2. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We found that 33% of patients in SAILS and HARP-2 were discordant by IL-18 level and LCA class. We further found that IL-18 level was only modestly correlated (0.17-0.47) with cytokines used in the LCA assignment. A substantial subset of individuals classified as hypoinflammatory by LCA (14% of SAILS and 43% of HARP-2) were classified as high risk by elevated IL-18. These individuals were at high risk for mortality in both SAILS (42% 60-d mortality, odds ratio [OR] 3.3; 95% CI, 1.8-6.1; p < 0.001) and HARP-2 (27% 60-d mortality, OR 2.1; 95% CI, 1.2-3.8; p = 0.009). CONCLUSIONS: Plasma IL-18 level provides important additional prognostic information to LCA subphenotypes defined largely by traditional inflammatory biomarkers in two large ARDS cohorts.


Subject(s)
Interleukin-18 , Respiratory Distress Syndrome , Humans , Latent Class Analysis , Retrospective Studies , Cytokines , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome/therapy , Biomarkers , Interleukin-8
15.
Int J Clin Pharm ; 45(5): 1167-1175, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37454025

ABSTRACT

BACKGROUND: Iatrogenic withdrawal syndrome, after exposure medication known to cause withdrawal is recognised, yet under described in adult intensive care. AIM: To investigate, opioid, sedation, and preadmission medication practice in critically ill adults with focus on aspects associated with iatrogenic withdrawal syndrome. METHOD: One-day point prevalence study in UK intensive care units (ICUs). We collected ICU admission medication and/or substances with withdrawal potential, sedation policy, opioid and sedative use, dose, and duration. RESULTS: Thirty-seven from 39 participating ICUs contributed data from 386 patients. The prevalence rate for parenteral opioid and sedative medication was 56.1% (212 patients). Twenty-three ICUs (59%) had no sedation/analgesia policy, and no ICUs screened for iatrogenic withdrawal. Patient admission medications with withdrawal-potential included antidepressants or antipsychotics (43, 20.3%) and nicotine (41, 19.3%). Of 212 patients, 202 (95.3%) received opioids, 163 (76.9%) sedatives and 153 (72.2%) both. Two hundred and two (95.3%) patients received opioids: 167 (82.7%) by continuous infusions and 90 (44.6%) patients for longer than 96-h. One hundred and sixty-three (76.9%) patients received sedatives: 157 (77.7%) by continuous infusions and 74 (45.4%) patients for longer than 96-h. CONCLUSION: Opioid sedative and admission medication with iatrogenic withdrawal syndrome potential prevalence rates were high, and a high proportion of ICUs had no sedative/analgesic policies. Nearly half of patients received continuous opioids and sedatives for longer than 96-h placing them at high risk of iatrogenic withdrawal. No participating unit reported using a validated tool for iatrogenic withdrawal assessment.


Subject(s)
Hypnotics and Sedatives , Substance Withdrawal Syndrome , Humans , Adult , Hypnotics and Sedatives/adverse effects , Analgesics, Opioid/adverse effects , Prevalence , Critical Illness/therapy , Substance Withdrawal Syndrome/epidemiology , Substance Withdrawal Syndrome/etiology , Iatrogenic Disease/epidemiology , United Kingdom/epidemiology
17.
Crit Care Med ; 51(7): 967-970, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37318291
18.
Intensive Care Med ; 49(7): 727-759, 2023 07.
Article in English | MEDLINE | ID: mdl-37326646

ABSTRACT

The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Adult , Humans , COVID-19/therapy , Respiration, Artificial , Positive-Pressure Respiration , Respiratory Distress Syndrome/therapy , Critical Care
19.
Am J Respir Crit Care Med ; 208(3): 256-269, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37154608

ABSTRACT

Rationale: Mesenchymal stromal cells (MSCs) may modulate inflammation, promoting repair in coronavirus disease (COVID-19)-related acute respiratory distress syndrome (ARDS). Objectives: We investigated the safety and efficacy of ORBCEL-C (CD362 [cluster of differentiation 362]-enriched, umbilical cord-derived MSCs) in COVID-19-related ARDS. Methods: In this multicenter, randomized, double-blind, allocation-concealed, placebo-controlled trial (NCT03042143), patients with moderate to severe COVID-19-related ARDS were randomized to receive ORBCEL-C (400 million cells) or placebo (Plasma-Lyte 148). The primary safety and efficacy outcomes were the incidence of serious adverse events and oxygenation index at Day 7, respectively. Secondary outcomes included respiratory compliance, driving pressure, PaO2:FiO2 ratio, and Sequential Organ Failure Assessment score. Clinical outcomes relating to duration of ventilation, lengths of ICU and hospital stays, and mortality were collected. Long-term follow-up included diagnosis of interstitial lung disease at 1 year and significant medical events and mortality at 2 years. Transcriptomic analysis was performed on whole blood at Days 0, 4, and 7. Measurements and Main Results: Sixty participants were recruited (final analysis: n = 30 received ORBCEL-C, n = 29 received placebo; 1 participant in the placebo group withdrew consent). Six serious adverse events occurred in the ORBCEL-C group and three in the placebo group (risk ratio, 2.9 [95% confidence interval, 0.6-13.2]; P = 0.25). Day 7 mean (SD) oxygenation index did not differ (ORBCEL-C, 98.3 [57.2] cm H2O/kPa; placebo, 96.6 [67.3] cm H2O/kPa). There were no differences in secondary surrogate outcomes or in mortality at Day 28, Day 90, 1 year, or 2 years. There was no difference in the prevalence of interstitial lung disease at 1 year or significant medical events up to 2 years. ORBCEL-C modulated the peripheral blood transcriptome. Conclusion: ORBCEL-C MSCs were safe in subjects with moderate to severe COVID-19-related ARDS but did not improve surrogates of pulmonary organ dysfunction.


Subject(s)
COVID-19 , Lung Diseases, Interstitial , Respiratory Distress Syndrome , Humans , Lung , Stromal Cells
20.
Nurs Crit Care ; 28(5): 773-780, 2023 09.
Article in English | MEDLINE | ID: mdl-37125669

ABSTRACT

BACKGROUND: The importance of good oral hygiene for patients in Intensive Care Units (ICUs) is well recognized, however, the most effective way to achieve good oral care in the ICU is unclear. AIM: This study aimed to provide a national picture of oral care practices in adult ICUs in the United Kingdom (UK) to identify areas for improvement. STUDY DESIGN: A national one-day point prevalence study was undertaken in adult ICUs in the UK in the period from 30th September to 14th October 2021. Data were collected on all patients in the ICU on the date of data collection. Using a validated electronic data collection form, anonymised data were collected on methods and frequency of oral care provided, and the use of oral care protocols within the ICU. Data were analysed using descriptive analysis. RESULTS: Data from 195 patients in 15 ICUs in England, Wales and Northern Ireland were collected. Written oral care protocols were available for use in the care of 65% (n = 127) of patients. 73% (n = 142) of patients received oral care within the 24-h period. Oral care methods included toothbrushing 41% (n = 79), foam sticks 3% (n = 5), moisturizing the oral cavity 10% (n = 19) and mouth rinse with chlorhexidine 3% (n = 5) and other oral care methods not specified 12% (n = 23). 44% (n = 85) of patients had an oral assessment within the 24-h period and variable assessment methods were used. CONCLUSION: There is large variability in oral care provision and methods for intubated ICU patients and a lack of consensus was revealed in the study. Oral assessment is conducted less frequently using multiple tools. Optimal oral care standards and further research into oral care provision is pivotal to address this important patient-relevant practice. RELEVANCE TO CLINICAL PRACTICE: Oral care is a fundamental part of care for ICU patients, however, there is a large degree of variability, and oral care is often not based upon oral assessment. The use of an oral care protocol and oral assessments would help to improve patient care, ease of use for staff and provide a tailored oral care plan for patients, improving efficiency and preventing wasted resources.


Subject(s)
Oral Hygiene , Pneumonia, Ventilator-Associated , Humans , Adult , Oral Hygiene/methods , Oral Health , Prevalence , Pneumonia, Ventilator-Associated/prevention & control , Intensive Care Units , Delivery of Health Care
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