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1.
Am J Respir Crit Care Med ; 209(2): 164-174, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-37938162

ABSTRACT

Rationale: Respiratory metagenomics (RMg) needs evaluation in a pilot service setting to determine utility and inform implementation into routine clinical practice. Objectives: Feasibility, performance, and clinical impacts on antimicrobial prescribing and infection control were recorded during a pilot RMg service. Methods: RMg was performed on 128 samples from 87 patients with suspected lower respiratory tract infection (LRTI) on two general and one specialist respiratory ICUs at Guy's and St Thomas' NHS Foundation Trust, London. Measurements and Main Results: During the first 15 weeks, RMg provided same-day results for 110 samples (86%), with a median turnaround time of 6.7 hours (interquartile range = 6.1-7.5 h). RMg was 93% sensitive and 81% specific for clinically relevant pathogens compared with routine testing. Forty-eight percent of RMg results informed antimicrobial prescribing changes (22% escalation; 26% deescalation) with escalation based on speciation in 20 out of 24 cases and detection of acquired-resistance genes in 4 out of 24 cases. Fastidious or unexpected organisms were reported in 21 samples, including anaerobes (n = 12), Mycobacterium tuberculosis, Tropheryma whipplei, cytomegalovirus, and Legionella pneumophila ST1326, which was subsequently isolated from the bedside water outlet. Application to consecutive severe community-acquired LRTI cases identified Staphylococcus aureus (two with SCCmec and three with luk F/S virulence determinants), Streptococcus pyogenes (emm1-M1uk clone), S. dysgalactiae subspecies equisimilis (STG62647A), and Aspergillus fumigatus with multiple treatments and public health impacts. Conclusions: This pilot study illustrates the potential of RMg testing to provide benefits for antimicrobial treatment, infection control, and public health when provided in a real-world critical care setting. Multicenter studies are now required to inform future translation into routine service.


Subject(s)
Anti-Infective Agents , Respiratory Tract Infections , Humans , Pilot Projects , London , Intensive Care Units , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/drug therapy
2.
Mycopathologia ; 189(3): 41, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38704761

ABSTRACT

BACKGROUND: The global prevalence of invasive fungal infections (IFI) is increasing, particularly within Intensive Care Units (ICU), where Candida spp. and Aspergillus spp. represent the most important pathogens. Diagnosis and management of IFIs becomes progressively challenging, with increasing antifungal resistance and the emergence of rare fungal species. Through a consensus survey focused on assessing current views on how IFI should be managed, the aim of this project was to identify challenges around diagnosing and managing IFIs in the ICU. The current status in different countries and perceived challenges to date amongst a multidisciplinary cohort of healthcare professionals involved in the care of IFI in the ICU was assessed. METHODS: Using a modified Delphi approach, an expert panel developed 44 Likert-scale statements across 6 key domains concerning patient screening and minimal standards for diagnosis of IFIs in ICU; initiation and termination of antifungal treatments and how to minimise their side effects and insights for future research on this topic. These were used to develop an online survey which was distributed on a convenience sampling basis utilising the subscriber list held by an independent provider (M3 Global). This survey was distributed to intensivists, infectious disease specialists, microbiologists and antimicrobial/ICU pharmacists within the UK, Germany, Spain, France and Italy. The threshold for consensus was set at 75%. RESULTS: A total of 335 responses were received during the five-month collection period. From these, 29/44 (66%) statements attained very high agreement (≥ 90%), 11/44 (25%) high agreement (< 90% and ≥ 75%), and 4/44 (9%) did not meet threshold for consensus (< 75%). CONCLUSION: The results outline the need for physicians to be aware of the local incidence of IFI and the associated rate of azole resistance in their ICUs. Where high clinical suspicion exists, treatment should start immediately and prior to receiving the results from any diagnostic test. Beta-D-glucan testing should be available to all ICU centres, with results available within 48 h to inform the cessation of empirical antifungal therapy. These consensus statements and proposed measures may guide future areas for further research to optimise the management of IFIs in the ICU.


Subject(s)
Antifungal Agents , Intensive Care Units , Invasive Fungal Infections , Humans , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/diagnosis , Antifungal Agents/therapeutic use , Europe , Surveys and Questionnaires , Consensus , Disease Management
3.
Thorax ; 79(1): 75-82, 2023 12 15.
Article in English | MEDLINE | ID: mdl-37657925

ABSTRACT

BACKGROUND: Invasive pulmonary aspergillosis is a complication of severe COVID-19, with regional variation in reported incidence and mortality. We describe the incidence, risk factors and mortality associated with COVID-19-associated pulmonary aspergillosis (CAPA) in a prospective, multicentre UK cohort. METHODS: From March 2020 to March 2021, 266 mechanically ventilated adults with COVID-19 were enrolled across 5 UK hospital intensive care units (ICUs). CAPA was defined using European Confederation for Medical Mycology and the International Society for Human and Animal Mycology criteria and fungal diagnostics performed on respiratory and serum samples. RESULTS: Twenty-nine of 266 patients (10.9%) had probable CAPA, 14 (5.2%) possible CAPA and none proven CAPA. Probable CAPA was diagnosed a median of 9 (IQR 7-16) days after ICU admission. Factors associated with probable CAPA after multivariable logistic regression were cumulative steroid dose given within 28 days prior to ICU admission (adjusted OR (aOR) 1.16; 95% CI 1.01 to 1.43 per 100 mg prednisolone-equivalent), receipt of an interleukin (IL)-6 inhibitor (aOR 2.79; 95% CI 1.22 to 6.48) and chronic obstructive pulmonary disease (COPD) (aOR 4.78; 95% CI 1.13 to 18.13). Mortality in patients with probable CAPA was 55%, vs 46% in those without. After adjustment for immortal time bias, CAPA was associated with an increased risk of 90-day mortality (HR 1.85; 95% CI 1.07 to 3.19); however, this association did not remain statistically significant after further adjustment for confounders (adjusted HR 1.57; 95% CI 0.88 to 2.80). There was no difference in mortality between patients with CAPA prescribed antifungals (9 of 17; 53%) and those who were not (7 of 12; 58%) (p=0.77). INTERPRETATION: In this first prospective UK study, probable CAPA was associated with corticosteroid use, receipt of IL-6 inhibitors and pre-existing COPD. CAPA did not impact mortality following adjustment for prognostic variables.


Subject(s)
COVID-19 , Pulmonary Aspergillosis , Pulmonary Disease, Chronic Obstructive , Adult , Animals , Humans , COVID-19/complications , Prospective Studies , Respiration, Artificial/adverse effects , Pulmonary Aspergillosis/epidemiology , United Kingdom/epidemiology
4.
Eur Respir J ; 61(2)2023 02.
Article in English | MEDLINE | ID: mdl-36229048

ABSTRACT

BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology and severity of COVID-19. METHODS: In this randomised, sequential, multicentre, placebo-controlled, double-blind study, adults aged 18-79 years (Part 1) or ≥70 years (Part 2) with severe COVID-19, respiratory failure and systemic inflammation (elevated C-reactive protein/ferritin) received a single intravenous infusion of otilimab 90 mg (human anti-GM-CSF monoclonal antibody) plus standard care (NCT04376684). The primary outcome was the proportion of patients alive and free of respiratory failure at Day 28. RESULTS: In Part 1 (n=806 randomised 1:1 otilimab:placebo), 71% of otilimab-treated patients were alive and free of respiratory failure at Day 28 versus 67% who received placebo; the model-adjusted difference of 5.3% was not statistically significant (95% CI -0.8-11.4%, p=0.09). A nominally significant model-adjusted difference of 19.1% (95% CI 5.2-33.1%, p=0.009) was observed in the predefined 70-79 years subgroup, but this was not confirmed in Part 2 (n=350 randomised) where the model-adjusted difference was 0.9% (95% CI -9.3-11.2%, p=0.86). Compared with placebo, otilimab resulted in lower serum concentrations of key inflammatory markers, including the putative pharmacodynamic biomarker CC chemokine ligand 17, indicative of GM-CSF pathway blockade. Adverse events were comparable between groups and consistent with severe COVID-19. CONCLUSIONS: There was no significant difference in the proportion of patients alive and free of respiratory failure at Day 28. However, despite the lack of clinical benefit, a reduction in inflammatory markers was observed with otilimab, in addition to an acceptable safety profile.


Subject(s)
COVID-19 , Respiratory Insufficiency , Adult , Humans , Granulocyte-Macrophage Colony-Stimulating Factor , Antibodies, Monoclonal, Humanized , Double-Blind Method , Treatment Outcome
5.
PLoS Pathog ; 17(9): e1009804, 2021 09.
Article in English | MEDLINE | ID: mdl-34529726

ABSTRACT

Prior studies have demonstrated that immunologic dysfunction underpins severe illness in COVID-19 patients, but have lacked an in-depth analysis of the immunologic drivers of death in the most critically ill patients. We performed immunophenotyping of viral antigen-specific and unconventional T cell responses, neutralizing antibodies, and serum proteins in critically ill patients with SARS-CoV-2 infection, using influenza infection, SARS-CoV-2-convalescent health care workers, and healthy adults as controls. We identify mucosal-associated invariant T (MAIT) cell activation as an independent and significant predictor of death in COVID-19 (HR = 5.92, 95% CI = 2.49-14.1). MAIT cell activation correlates with several other mortality-associated immunologic measures including broad activation of CD8+ T cells and non-Vδ2 γδT cells, and elevated levels of cytokines and chemokines, including GM-CSF, CXCL10, CCL2, and IL-6. MAIT cell activation is also a predictor of disease severity in influenza (ECMO/death HR = 4.43, 95% CI = 1.08-18.2). Single-cell RNA-sequencing reveals a shift from focused IFNα-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 -a feature not observed in severe influenza. We conclude that fatal COVID-19 infection is driven by uncoordinated inflammatory responses that drive a hierarchy of T cell activation, elements of which can serve as prognostic indicators and potential targets for immune intervention.


Subject(s)
COVID-19/immunology , COVID-19/mortality , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antigens, CD/immunology , Antigens, Differentiation, T-Lymphocyte/immunology , B-Lymphocytes/immunology , Biomarkers/blood , Blood Proteins/metabolism , Cohort Studies , Critical Illness/mortality , Female , Humans , Immunophenotyping , Influenza, Human/immunology , Lectins, C-Type/immunology , Lymphocyte Activation , Male , Middle Aged , Mucosal-Associated Invariant T Cells/immunology , Patient Acuity
6.
Clin Infect Dis ; 74(10): 1795-1803, 2022 05 30.
Article in English | MEDLINE | ID: mdl-34420048

ABSTRACT

BACKGROUND: An endotracheal tube cuff pressure between 20 and 30 cmH2O is recommended to prevent ventilator-associated respiratory infection (VARI). We aimed to evaluate whether continuous cuff pressure control (CPC) was associated with reduced VARI incidence compared with intermittent CPC. METHODS: We conducted a multicenter open-label randomized controlled trial in intensive care unit (ICU) patients within 24 hours of intubation in Vietnam. Patients were randomly assigned 1:1 to receive either continuous CPC using an automated electronic device or intermittent CPC using a manually hand-held manometer. The primary endpoint was the occurrence of VARI, evaluated by an independent reviewer blinded to the CPC allocation. RESULTS: We randomized 600 patients; 597 received the intervention or control and were included in the intention to treat analysis. Compared with intermittent CPC, continuous CPC did not reduce the proportion of patients with at least one episode of VARI (74/296 [25%] vs 69/301 [23%]; odds ratio [OR] 1.13; 95% confidence interval [CI] .77-1.67]. There were no significant differences between continuous and intermittent CPC concerning the proportion of microbiologically confirmed VARI (OR 1.40; 95% CI .94-2.10), the proportion of intubated days without antimicrobials (relative proportion [RP] 0.99; 95% CI .87-1.12), rate of ICU discharge (cause-specific hazard ratio [HR] 0.95; 95% CI .78-1.16), cost of ICU stay (difference in transformed mean [DTM] 0.02; 95% CI -.05 to .08], cost of ICU antimicrobials (DTM 0.02; 95% CI -.25 to .28), cost of hospital stay (DTM 0.02; 95% CI -.04 to .08), and ICU mortality risk (OR 0.96; 95% CI .67-1.38). CONCLUSIONS: Maintaining CPC through an automated electronic device did not reduce VARI incidence. CLINICAL TRIAL REGISTRATION: NCT02966392.


Subject(s)
Pneumonia, Ventilator-Associated , Respiratory Tract Infections , Humans , Intubation, Intratracheal/adverse effects , Length of Stay , Pneumonia, Ventilator-Associated/epidemiology , Pneumonia, Ventilator-Associated/microbiology , Pneumonia, Ventilator-Associated/prevention & control , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/prevention & control , Ventilators, Mechanical
7.
Crit Care Med ; 49(4): 697-701, 2021 04 01.
Article in English | MEDLINE | ID: mdl-33395069

ABSTRACT

OBJECTIVES: Candida auris has been implicated in ICU outbreaks worldwide and is notable for being difficult to identify and treat, its resilience in the environment, and significant patient mortality associated with invasive disease. Here, we describe a small C. auris outbreak and how it was terminated. DESIGN: Single-center, observational. SETTING: Two general adult ICUs at an urban U.K. teaching hospital. PATIENTS: All patients positive for C. auris during the 5-month outbreak were included (n = 7). INTERVENTIONS: Stepwise implementation of enhanced infection prevention and control precautions was introduced including twice-weekly screening, contact tracing, isolation precautions, and environmental decontamination. A detailed environmental screen was performed to identify potential reservoirs. This included the patient bed space and clinical equipment and a frequently handled cloth lanyard attached to a key used to access controlled drugs. Personal possessions such as mobile phones, lanyards, and identification badges were also screened. MEASUREMENTS AND MAIN RESULTS: The index case and six linked acquisitions were identified. Four of six (67%) patients were identified after discharge of all known previous C. auris cases from ICU, highlighting potential for an environmental reservoir. Environmental screening identified C. auris from a patient bed space following deep cleaning, prompting review and enhancement of cleaning procedures. The controlled drug cloth lanyard was positive for C. auris, which prompted removal and culture of all staff lanyards. C. auris was identified on 1/100 staff lanyards (1%). No mobile phones or identification badges were positive for C. auris. The outbreak terminated following withdrawal of lanyards from ICU. CONCLUSIONS: This outbreak further implicates environmental reservoirs as sustaining C. auris ICU outbreaks. Identification of C. auris on cloth lanyards highlights the need to identify commonly handled moveable objects during an outbreak. We suggest that ICUs with a C. auris outbreak should investigate similar infrequently cleaned items as potential reservoirs and review their policies on lanyard use.


Subject(s)
Antifungal Agents/therapeutic use , Clothing/adverse effects , Drug Resistance, Fungal , Infection Control/methods , Adult , Candida , Disease Transmission, Infectious/prevention & control , Female , Humans , Intensive Care Units , Male , Microbial Sensitivity Tests , Middle Aged
8.
Crit Care ; 25(1): 151, 2021 04 20.
Article in English | MEDLINE | ID: mdl-33879189

ABSTRACT

BACKGROUND: The early recognition and management of sepsis improves outcomes. Biomarkers may help in identifying earlier sub-clinical signs of sepsis. We explored the potential of serial measurements of C-reactive protein (CRP), procalcitonin (PCT) and pancreatic stone protein (PSP) for the early recognition of sepsis in patients hospitalized in the intensive care unit (ICU). METHODS: This was a multicentric international prospective observational clinical study conducted in 14 ICUs in France, Switzerland, Italy, and the United Kingdom. Adult ICU patients at risk of nosocomial sepsis were included. A biomarker-blinded adjudication committee identified sepsis events and the days on which they began. The association of clinical sepsis diagnoses with the trajectories of PSP, CRP, and PCT in the 3 days preceding these diagnoses of sepsis were tested for markers of early sepsis detection. The performance of the biomarkers in sepsis diagnosis was assessed by receiver operating characteristic (ROC) analysis. RESULTS: Of the 243 patients included, 53 developed nosocomial sepsis after a median of 6 days (interquartile range, 3-8 days). Clinical sepsis diagnosis was associated with an increase in biomarkers value over the 3 days preceding this diagnosis [PSP (p = 0.003), PCT (p = 0.025) and CRP (p = 0.009)]. PSP started to increase 5 days before the clinical diagnosis of sepsis, PCT 3 and CRP 2 days, respectively. The area under the ROC curve at the time of clinical sepsis was similar for all markers (PSP, 0.75; CRP, 0.77; PCT, 0.75). CONCLUSIONS: While the diagnostic accuracy of PSP, CRP and PCT for sepsis were similar in this cohort, serial PSP measurement demonstrated an increase of this marker the days preceding the onset of signs necessary to clinical diagnose sepsis. This observation justifies further evaluation of the potential clinical benefit of serial PSP measurement in the management of critically ill patients developing nosocomial sepsis. Trial registration The study has been registered at ClinicalTrials.gov (no. NCT03474809), on March 16, 2018. https://www.clinicaltrials.gov/ct2/show/NCT03474809?term=NCT03474809&draw=2&rank=1 .


Subject(s)
Lithostathine/analysis , Sepsis/diagnosis , Aged , Area Under Curve , Biomarkers/analysis , Female , France/epidemiology , Humans , Intensive Care Units/organization & administration , Intensive Care Units/statistics & numerical data , Italy/epidemiology , Male , Middle Aged , Organ Dysfunction Scores , Prospective Studies , ROC Curve , Sepsis/epidemiology , Switzerland/epidemiology , United Kingdom/epidemiology
9.
Eur Arch Otorhinolaryngol ; 278(5): 1595-1604, 2021 May.
Article in English | MEDLINE | ID: mdl-32740720

ABSTRACT

PURPOSE: COVID-19 patients requiring mechanical ventilation can overwhelm existing bed capacity. We aimed to better understand the factors that influence the trajectory of tracheostomy care in this population to facilitate capacity planning and improve outcomes. METHODS: We conducted an observational cohort study of patients in a high-volume centre in the worst-affected region of the UK including all patients that underwent tracheostomy for COVID-19 pneumonitis ventilatory wean from 1st March 2020 to 10th May 2020. The primary outcome was time from insertion to decannulation. The analysis utilised Cox regression to account for patients that are still progressing through their tracheostomy pathway. RESULTS: At the point of analysis, a median 21 days (IQR 15-28) post-tracheostomy and 39 days (IQR 32-45) post-intubation, 35/69 (57.4%) patients had been decannulated a median of 17 days (IQR 12-20.5) post-insertion. The overall median age was 55 (IQR 48-61) with a male-to-female ratio of 2:1. In Cox regression analysis, FiO2 at tracheostomy ≥ 0.4 (HR 1.80; 95% CI 0.89-3.60; p = 0.048) and last pre-tracheostomy peak cough flow (HR 2.27; 95% CI 1.78-4.45; p = 0.001) were independent variables associated with prolonged time to decannulation. CONCLUSION: Higher FiO2 at tracheostomy and higher pre-tracheostomy peak cough flow are associated with increased delay in COVID-19 tracheostomy patient decannulation. These finding comprise the most comprehensive report of COVID-19 tracheostomy decannulation to date and will assist service planning for future peaks of this pandemic.


Subject(s)
COVID-19 , Tracheostomy , Device Removal , Female , Humans , Male , Middle Aged , Respiration, Artificial , SARS-CoV-2
10.
Eur Arch Otorhinolaryngol ; 277(8): 2173-2184, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32314050

ABSTRACT

PURPOSE: The COVID-19 pandemic is placing unprecedented demand upon critical care services for invasive mechanical ventilation. There is current uncertainty regarding the role of tracheostomy for weaning ventilated patients with COVID-19 pneumonia. This is due to a number of factors including prognosis, optimal healthcare resource utilisation, and safety of healthcare workers when performing such a high-risk aerosol-generating procedure. METHODS: Literature review and proposed practical guideline based on the experience of a tertiary healthcare institution with 195 critical care admissions for COVID-19 up until 4th April 2020. RESULTS: A synthesis of the current international literature and reported experience is presented with respect to prognosis, viral load and staff safety, thus leading to a pragmatic recommendation that tracheostomy is not performed until at least 14 days after endotracheal intubation in COVID-19 patients. Practical steps to minimise aerosol generation in percutaneous tracheostomy are outlined and we describe the process and framework for setting up a dedicated tracheostomy team. CONCLUSION: In selected COVID-19 patients, there is a role for tracheostomy to aid in weaning and optimise healthcare resource utilisation. Both percutaneous and open techniques can be performed safely with careful modifications to technique and appropriate enhanced personal protective equipment. ORL-HNS surgeons can play a valuable role in forming tracheostomy teams to support critical care teams during this global pandemic.


Subject(s)
Infectious Disease Transmission, Patient-to-Professional/prevention & control , Intubation, Intratracheal , Practice Guidelines as Topic , Respiration, Artificial , Tracheostomy/methods , Aerosols , Betacoronavirus , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Humans , Intubation, Intratracheal/standards , Pandemics/prevention & control , Personal Protective Equipment , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Respiration, Artificial/standards , SARS-CoV-2 , Tracheostomy/standards
11.
Clin Infect Dis ; 68(11): 1932-1934, 2019 05 17.
Article in English | MEDLINE | ID: mdl-30418554

ABSTRACT

Serious infections such as endocarditis due to extremely drug-resistance gram-negative bacteria are an increasing challenge. Here, we present successful adjunctive use of cefiderocol for a patient with persistently bacteremic healthcare-associated native aortic valve endocarditis due to an extended-spectrum beta-lactamase-positive Pseudomonas aeruginosa susceptible in vitro only to colistin, following failure of conventional therapeutic options.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Aortic Valve/microbiology , Cephalosporins/therapeutic use , Drug Resistance, Multiple, Bacterial , Endocarditis, Bacterial/drug therapy , Pseudomonas Infections/drug therapy , Aged , Colistin/pharmacology , Compassionate Use Trials , Endocarditis, Bacterial/microbiology , Female , Humans , Microbial Sensitivity Tests , Pseudomonas Infections/complications , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/enzymology , Treatment Outcome , beta-Lactamases , Cefiderocol
12.
Crit Care Med ; 47(9): 1177-1183, 2019 09.
Article in English | MEDLINE | ID: mdl-31419216

ABSTRACT

OBJECTIVES: Quantification of potential for lung recruitment may guide the ventilatory strategy in acute respiratory distress syndrome. However, there are no quantitative data on recruitability in patients with severe acute respiratory distress syndrome who require extracorporeal membrane oxygenation. We sought to quantify potential for lung recruitment and its relationship with outcomes in this cohort of patients. DESIGN: A single-center, retrospective, observational cohort study. SETTING: Tertiary referral severe respiratory failure center in a university hospital in the United Kingdom. PATIENTS: Forty-seven adults with severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: In patients with severe acute respiratory distress syndrome-mainly of pulmonary origin (86%)-the potential for lung recruitment and the weight of nonaerated, poorly aerated, normally aerated, and hyperaerated lung tissue were assessed at low (5 cmH2O) and high (45 cmH2O) airway pressures. Patients were categorized as high or low potential for lung recruitment based on the median potential for lung recruitment value of the study population. The median potential for lung recruitment was 24.3% (interquartile range = 11.4-37%) ranging from -2% to 76.3% of the total lung weight. Patients with potential for lung recruitment above the median had significantly shorter extracorporeal membrane oxygenation duration (8 vs 13 d; p = 0.013) and shorter ICU stay (15 vs 22 d; p = 0.028), but mortality was not statistically different (24% vs 46%; p = 0.159). CONCLUSIONS: We observed significant variability in potential for lung recruitment in patients with severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation. Patients with high potential for lung recruitment had a shorter ICU stay and shorter extracorporeal membrane oxygenation duration.


Subject(s)
Extracorporeal Membrane Oxygenation/methods , Lung/physiopathology , Positive-Pressure Respiration/methods , Respiratory Distress Syndrome/physiopathology , Respiratory Distress Syndrome/therapy , Adolescent , Adult , Aged , Female , Humans , Intensive Care Units/statistics & numerical data , Length of Stay/statistics & numerical data , Lung Compliance/physiology , Male , Middle Aged , Organ Size , Respiration, Artificial/methods , Retrospective Studies , Tertiary Care Centers , Time Factors , United Kingdom , Young Adult
13.
Crit Care ; 22(1): 215, 2018 Sep 19.
Article in English | MEDLINE | ID: mdl-30231909

ABSTRACT

Despite timely intervention, there exists a small subgroup of patients with septic shock who develop progressive multi-organ failure. Seemingly refractory to conventional therapy, they exhibit a very high mortality. Such patients are often poorly represented in large clinical trials. Consequently, good evidence for effective treatment strategies is lacking. In this article, we describe a pragmatic, multi-faceted approach to managing patients with refractory septic shock based on our experience of toxin-mediated sepsis in a specialist referral centre. Many components of this strategy are inexpensive and widely accessible, and so may offer an opportunity to improve outcomes in these critically ill patients.


Subject(s)
Shock, Septic/classification , Shock, Septic/drug therapy , Adrenal Cortex Hormones/pharmacology , Adrenal Cortex Hormones/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cardiotonic Agents/pharmacology , Cardiotonic Agents/therapeutic use , Extracorporeal Membrane Oxygenation/methods , Humans , Immunoglobulins/pharmacology , Immunoglobulins/therapeutic use , Multiple Organ Failure/prevention & control , Renal Replacement Therapy/methods , Serum Albumin, Human/pharmacology , Serum Albumin, Human/therapeutic use , Simendan/pharmacology , Simendan/therapeutic use , Treatment Outcome , Vasoconstrictor Agents/pharmacology , Vasoconstrictor Agents/therapeutic use
16.
Crit Care Med ; 45(10): 1642-1649, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28727576

ABSTRACT

OBJECTIVES: For patients supported with veno-venous extracorporeal membrane oxygenation, the occurrence of intracranial hemorrhage is associated with a high mortality. It is unclear whether intracranial hemorrhage is a consequence of the extracorporeal intervention or of the underlying severe respiratory pathology. In a cohort of patients transferred to a regional severe respiratory failure center that routinely employs admission brain imaging, we sought 1) the prevalence of intracranial hemorrhage; 2) survival and neurologic outcomes; and 3) factors associated with intracranial hemorrhage. DESIGN: A single-center, retrospective, observational cohort study. SETTING: Tertiary referral severe respiratory failure center, university teaching hospital. PATIENTS: Patients admitted between December 2011 and February 2016. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Three hundred forty-two patients were identified: 250 managed with extracorporeal support and 92 managed using conventional ventilation. The prevalence of intracranial hemorrhage was 16.4% in extracorporeal membrane oxygenation patients and 7.6% in conventionally managed patients (p = 0.04). Multivariate analysis revealed factors independently associated with intracranial hemorrhage to be duration of ventilation (d) (odds ratio, 1.13 [95% CI, 1.03-1.23]; p = 0.011) and admission fibrinogen (g/L) (odds ratio, 0.73 [0.57-0.91]; p = 0.009); extracorporeal membrane oxygenation was not an independent risk factor (odds ratio, 3.29 [0.96-15.99]; p = 0.088). In patients who received veno-venous extracorporeal membrane oxygenation, there was no significant difference in 6-month survival between patients with and without intracranial hemorrhage (68.3% vs 76.0%; p = 0.350). Good neurologic function was observed in 92%. CONCLUSIONS: We report a higher prevalence of intracranial hemorrhage than has previously been described with high level of neurologically intact survival. Duration of mechanical ventilation and admission fibrinogen, but not exposure to extracorporeal support, are independently associated with intracranial hemorrhage.


Subject(s)
Extracorporeal Membrane Oxygenation , Intracranial Hemorrhages/epidemiology , Respiratory Insufficiency/epidemiology , Adult , Cohort Studies , Female , Fibrinogen/analysis , Humans , Intensive Care Units , London/epidemiology , Male , Middle Aged , Multivariate Analysis , Respiration, Artificial , Retrospective Studies , Risk Factors , Severity of Illness Index , Time Factors
17.
Crit Care Med ; 44(7): e583-6, 2016 Jul.
Article in English | MEDLINE | ID: mdl-26807685

ABSTRACT

OBJECTIVES: Veno-venous extracorporeal membrane oxygenation is an increasingly used form of advanced respiratory support, but its effects on the physiology of the right heart are incompletely understood. We seek to illustrate the impact of veno-venous extracorporeal membrane oxygenation return blood flow upon the right atrium by considering the physiologic effects during interatrial shunting. PATIENTS: Two veno-venous extracorporeal membrane oxygenation patients in whom an extracorporeal membrane oxygenation induced right-to-left interatrial shunt appears to have created a barrier to liberation from extracorporeal support. CONCLUSIONS: Veno-venous extracorporeal membrane oxygenation return flow generates a high-pressure jet that has potential to exert focal pressure upon the intra-atrial septum. In patients with potential for interatrial flow, this may lead to a right-to-left shunt, which becomes physiologically apparent only when sweep gas flow is ceased.


Subject(s)
Extracorporeal Membrane Oxygenation , Heart Septal Defects , Heart/physiopathology , Respiratory Insufficiency/therapy , Adult , Echocardiography , Female , Heart/diagnostic imaging , Heart Septal Defects/diagnostic imaging , Heart Septal Defects/physiopathology , Humans , Male , Respiratory Insufficiency/physiopathology , Ventricular Pressure
18.
Crit Care ; 20: 52, 2016 Mar 08.
Article in English | MEDLINE | ID: mdl-26951090

ABSTRACT

BACKGROUND: In hospitalised patients, anaemia increases the risk of developing acute kidney injury (AKI). Our aim was to determine whether anaemia also has an impact on the risk of progression from early AKI to more severe AKI in critically ill patients. METHODS: We retrospectively analysed the data of patients admitted to the adult intensive care unit between 2007 and 2009 who had AKI I as per the AKI Network classification, and who had undergone haemodynamic monitoring within 12 h of AKI I. We collected baseline characteristics, severity of illness, haemoglobin (Hb), and haemodynamic parameters in the first 12 h of AKI I and differentiated between patients who progressed to AKI III and those who did not. Univariate and multivariate logistic regression analyses were used to identify risk factors for progression. Associations between Hb, arterial oxygen saturation and cardiac index were explored by receiver operating characteristic curve analysis. RESULTS: Two hundred and ten patients (median age 70 years, 68% male) underwent haemodynamic monitoring within 12 h of AKI I; 85 (41.5%) progressed to AKI III. The proportion of patients with underlying cardiac disease was significantly higher among progressors versus non-progressors (58% vs 34%, respectively; p = 0.001). On the first day of AKI I, progressors had a significantly higher Sequential Organ Failure Assessment score (9 vs 8; p < 0.001), lower cardiac index (median 2.6 vs 3.3 L/min/m(2); p < 0.001), higher arterial lactate (2 vs 1.6 mmol/L; p < 0.001), higher central venous pressure (16 vs 13; p = 0.02), lower mean arterial blood pressure (median 71 vs 74 mmHg; p = 0.01) and significantly higher requirement for cardiovascular and respiratory support, but there was no difference in Hb concentration (median 96 g/L in both groups). Multivariable regression analysis showed that heart disease, need for mechanical ventilation, arterial lactate, Sequential Organ Failure Assessment score, central venous pressure and cardiac index on first day of AKI I were independently associated with progression to AKI III. There was no significant difference in the risk of progression between patients with Hb ≤ or >80 g/L, and ≤ or >100 g/L on day of AKI I. CONCLUSIONS: In critically ill patients with AKI stage 1, anaemia was not associated with an increased risk of progression to more severe AKI.


Subject(s)
Acute Kidney Injury/etiology , Anemia/complications , Disease Progression , Aged , Aged, 80 and over , Female , Hemodynamics/physiology , Hospital Mortality , Humans , Intensive Care Units , Male , Middle Aged , Organ Dysfunction Scores , Regression Analysis , Retrospective Studies , Risk Factors
20.
Crit Care Med ; 43(12): e581-4, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26308437

ABSTRACT

OBJECTIVES: Venovenous extracorporeal membrane oxygenation for patients with severe respiratory failure is increasingly common. There has been a significant change in the population, technology, and approach used for venovenous extracorporeal membrane oxygenation over the last 10 years. The objective of this study is to describe the prevalence of postdecannulation deep vein thrombosis in the cannulated vessel in adults who have received venovenous extracorporeal membrane oxygenation for severe respiratory failure. DESIGN: A single-center, retrospective, observational cohort, electronic note review study. SETTING: Tertiary referral university teaching hospital. PATIENTS: Patients commenced on venovenous extracorporeal membrane oxygenation for severe respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 103 patients commenced on extracorporeal membrane oxygenation with 81 survivors from December 2011 to February 2014. We performed postdecannulation venous Doppler ultrasound in 88.9% of extracorporeal membrane oxygenation survivors. The prevalence of deep vein thrombosis in the cannulated vessel following extracorporeal membrane oxygenation is 8.1/1,000 cannula days in patients who were screened. CONCLUSIONS: The prevalence of deep vein thrombosis following decannulation from extracorporeal membrane oxygenation for severe respiratory failure is clinically significant, and routine venous Doppler ultrasound following decannulation is warranted in this population.


Subject(s)
Extracorporeal Membrane Oxygenation/adverse effects , Respiratory Insufficiency/therapy , Venous Thrombosis/etiology , Adult , Catheterization/methods , Female , Humans , Male , Middle Aged , Prevalence , Retrospective Studies , Severity of Illness Index , Tertiary Care Centers , Ultrasonography , Venous Thrombosis/diagnostic imaging
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