Clinical impact of screening computed tomography in extracorporeal membrane oxygenation: a retrospective cohort study.

BACKGROUND: Data on the prevalence and clinical impact of extrapulmonary findings at screening computed tomography (CT) on initiation of veno-venous extracorporeal membrane oxygenation (V-V ECMO) are limited. We aimed to identify the prevalence of extrapulmonary findings on screening CT following V-V ECMO initiation. We hypothesized that extrapulmonary findings would influence clinical management and outcome. METHODS: Retrospective analysis (2011-2021) of admission screening CT including head, abdomen and pelvis with contrast of consecutive patients on initiation of V-V ECMO. CT findings identified by the attending consultant radiologist were extracted. Demographics, admission physiological and laboratory data, clinical decision-making following CT and ECMO ICU mortality were recorded from the electronic medical record. We used multivariable logistic regression and Kaplan-Meier curves to evaluate associations between extrapulmonary findings and ECMO ICU mortality. RESULTS: Of the 833 patients receiving V-V ECMO, 761 underwent routine admission CT (91.4%). ECMO ICU length of stay was 19 days (IQR 12-23); ICU mortality at the ECMO centre was 18.9%. An incidental extrapulmonary finding was reported in 227 patients (29.8%), leading to an invasive procedure in 12/227 cases (5.3%) and a change in medical management (mainly in anticoagulation strategy) in 119/227 (52.4%). Extrapulmonary findings associated with mortality were intracranial haemorrhage (OR 2.34 (95% CI 1.31-4.12), cerebral infarction (OR 3.59 (95% CI 1.26-9.86) and colitis (OR 2.80 (95% CI 1.35-5.67). CONCLUSIONS: Screening CT frequently identifies extrapulmonary findings of clinical significance. Newly detected intracranial haemorrhage, cerebral infarction and colitis were associated with increased ICU mortality.

Prevalence and Indications for Oxygenator Circuit Replacement in Patients Receiving Venovenous Extracorporeal Membrane Oxygenation.

In this retrospective observational cohort study, we aimed to describe the rate of extracorporeal membrane oxygenation (ECMO) circuit change, the associated risk factors and its relationship with patient characteristics and outcome in patients receiving venovenous (VV) ECMO at our center between January 2015 and November 2017. Twenty-seven percent of the patients receiving VV ECMO (n = 224) had at least one circuit change, which was associated with lower ICU survival (68% vs 82% p=0.032) and longer ICU stay (30 vs . 17 days p < 0.001). Circuit duration was similar when stratified by gender, clinical severity, or prior circuit change. Hematological abnormalities and increased transmembrane lung pressure (TMLP) were the most frequent indication for circuit change. The change in transmembrane lung resistance (Δ TMLR) gave better prediction of circuit change than TMLP, TMLR, or ΔTMLP. Low postoxygenator PO 2 was indicated as a reason for one-third of the circuit changes. However, the ECMO oxygen transfer was significantly higher in cases of circuit change with documented "low postoxygenator PO 2 " than those without (244 ± 62 vs. 200 ± 57 ml/min; p = 0.009). The results suggest that circuit change in VV ECMO is associated with worse outcomes, that the Δ TMLR is a better predictor of circuit change than TMLP, and that the postoxygenator PO 2 is an unreliable proxy for the oxygenator function.

Acute liver failure.

PURPOSE OF REVIEW: Present an outline of acute liver failure, from its definition to its management in critical care, updated with findings of selected newer research. RECENT FINDINGS: Survival of patients with acute liver failure has progressively improved. Intracranial hypertension complicating hepatic encephalopathy is now much less frequent than in the past and invasive ICP monitoring is now rarely used. Early renal replacement therapy and possibly therapeutic plasma exchange have consolidated their role in the treatment. Further evidence confirms the low incidence of bleeding in these patients despite striking abnormalities in standard tests of coagulation and new findings of abnormalities on thromboelastographic testing. Specific coagulopathy profiles including an abnormal vWF/ADAMTS13 ratio may be associated with poor outcome and increased bleeding risk. Use of N-acetylcysteine in nonparacetamol-related cases remains unsupported by robust clinical evidence. New microRNA-based prognostic markers to select patients for transplantation are described but are still far from widespread clinical applicability; imaging-based prognostication tools are also promising. The use of extracorporeal artificial liver devices in clinical practice is yet to be supported by evidence. SUMMARY: Medical treatment of patients with acute liver failure is now associated with significantly improved survival. Better prognostication and selection for emergency liver transplant may further improve care for these patients.

Positive End-Expiratory Pressure and Respiratory Rate Modify the Association of Mechanical Power and Driving Pressure With Mortality Among Patients With Acute Respiratory Distress Syndrome.

IMPORTANCE: Mechanical power and driving pressure have known associations with survival for patients with acute respiratory distress syndrome. OBJECTIVES: To further understand the relative importance of mechanical power and driving pressure as clinical targets for ventilator management. DESIGN: Secondary observational analysis of randomized clinical trial data. SETTING AND PARTICIPANTS: Patients with the acute respiratory distress syndrome from three Acute Respiratory Distress Syndrome Network trials. MAIN OUTCOMES AND MEASURES: After adjusting for patient severity in a multivariate Cox proportional hazards model, we examined the relative association of driving pressure and mechanical power with hospital mortality. Among 2,410 patients, the relationship between driving pressure and mechanical power with mortality was modified by respiratory rate, positive end-expiratory pressure, and flow. RESULTS: Among patients with low respiratory rate (< 26), only power was significantly associated with mortality (power [hazard ratio, 1.82; 95% CI, 1.41-2.35; p < 0.001] vs driving pressure [hazard ratio, 1.01; 95% CI, 0.84-1.21; p = 0.95]), while among patients with high respiratory rate, neither was associated with mortality. Both power and driving pressure were associated with mortality at high airway flow (power [hazard ratio, 1.28; 95% CI, 1.15-1.43; p < 0.001] vs driving pressure [hazard ratio, 1.15; 95% CI, 1.01-1.30; p = 0.041]) and neither at low flow. At low positive end-expiratory pressure, neither was associated with mortality, whereas at high positive end-expiratory pressure (≥ 10 cm H2O), only power was significantly associated with mortality (power [hazard ratio, 1.22; 95% CI, 1.09-1.37; p < 0.001] vs driving pressure [hazard ratio, 1.16; 95% CI, 0.99-1.35; p = 0.059]). CONCLUSIONS AND RELEVANCE: The relationship between mechanical power and driving pressure with mortality differed within severity subgroups defined by positive end-expiratory pressure, respiratory rate, and airway flow.

Albumin Oxidation Status in Sepsis Patients Treated With Albumin or Crystalloids.

Inflammation and oxidative stress characterize sepsis and determine its severity. In this study, we investigated the relationship between albumin oxidation and sepsis severity in a selected cohort of patients from the Albumin Italian Outcome Study (ALBIOS). A retrospective analysis was conducted on the oxidation forms of human albumin [human mercapto-albumin (HMA), human non-mercapto-albumin form 1 (HNA1) and human non-mercapto-albumin form 2 (HNA2)] in 60 patients with severe sepsis or septic shock and 21 healthy controls. The sepsis patients were randomized (1:1) to treatment with 20% albumin and crystalloid solution or crystalloid solution alone. The albumin oxidation forms were measured at day 1 and day 7. To assess the albumin oxidation forms as a function of oxidative stress, the 60 sepsis patients, regardless of the treatment, were grouped based on baseline sequential organ failure assessment (SOFA) score as surrogate marker of oxidative stress. At day 1, septic patients had significantly lower levels of HMA and higher levels of HNA1 and HNA2 than healthy controls. HMA and HNA1 concentrations were similar in patients treated with albumin or crystalloids at day 1, while HNA2 concentration was significantly greater in albumin-treated patients (p < 0.001). On day 7, HMA was significantly higher in albumin-treated patients, while HNA2 significantly increased only in the crystalloids-treated group, reaching values comparable with the albumin group. When pooling the septic patients regardless of treatment, albumin oxidation was similar across all SOFA groups at day 1, but at day 7 HMA was lower at higher SOFA scores. Mortality rate was independently associated with albumin oxidation levels measured at day 7 (HMA log-rank = 0.027 and HNA2 log-rank = 0.002), irrespective of treatment group. In adjusted regression analyses for 90-day mortality, this effect remained significant for HMA and HNA2. Our data suggest that the oxidation status of albumin is modified according to the time of exposure to oxidative stress (differences between day 1 and day 7). After 7 days of treatment, lower SOFA scores correlate with higher albumin antioxidant capacity. The trend toward a positive effect of albumin treatment, while not statistically significant, warrants further investigation.

A survey on the practices and capabilities in the management of respiratory failure in South East England.

INTRODUCTION: The variability of acute respiratory distress syndrome management may affect the referral practice to severe respiratory failure centres. We described the management of acute respiratory distress syndrome in our catchment area. METHODS: An electronic survey was administered to 42 intensive care units in South-East England. RESULTS: Response rate was 71.4%. High-flow nasal oxygen and non-invasive ventilation were used 'often' in moderate-acute respiratory distress syndrome by 46.7% and 60%. During invasive ventilation, 90% preferred pressure control, targeting tidal volumes of 6-8 ml/kg (53.3%) or 4-6 ml/kg (46.7%). Positive end-expiratory pressure was selected by positive end-expiratory pressure/inspiratory fraction of oxygen tables (50%) or decremental positive end-expiratory pressure trials (20%). Neuro-muscular blockers were widely used, although routinely by only 3.3%. High-frequency oscillatory ventilation (10%) and inhaled nitric oxide (13.3%) were rarely used. None used oesophageal manometry. Recruitment manoeuvres were used 'often' by 26.7%. Equipment (90%) and protocols (80%) for prone position were common, with sessions mostly lasting 12-18 h. CONCLUSIONS: Although variable, practice well reflected the available evidence. Proning was widely practiced with good availability of educational resources and protocolised care.

Physiological Basis of Extracorporeal Membrane Oxygenation and Extracorporeal Carbon Dioxide Removal in Respiratory Failure.

Extracorporeal life support (ECLS) for severe respiratory failure has seen an exponential growth in recent years. Extracorporeal membrane oxygenation (ECMO) and extracorporeal CO2 removal (ECCO2R) represent two modalities that can provide full or partial support of the native lung function, when mechanical ventilation is either unable to achieve sufficient gas exchange to meet metabolic demands, or when its intensity is considered injurious. While the use of ECMO has defined indications in clinical practice, ECCO2R remains a promising technique, whose safety and efficacy are still being investigated. Understanding the physiological principles of gas exchange during respiratory ECLS and the interactions with native gas exchange and haemodynamics are essential for the safe applications of these techniques in clinical practice. In this review, we will present the physiological basis of gas exchange in ECMO and ECCO2R, and the implications of their interaction with native lung function. We will also discuss the rationale for their use in clinical practice, their current advances, and future directions.

Initial setting of high-flow nasal oxygen post extubation based on mean inspiratory flow during a spontaneous breathing trial.

PURPOSE: High flow nasal cannula (HFNC) is commonly used post-extubation in intensive care (ICU). Patients' comfort during HFNC is affected by flow rate. The study aims to describe the relationship between pre-extubation inspiratory flow requirements and the post-extubation flow rates on HFNC that maximises patient's comfort. METHODS: This was an observational, retrospective study conducted in a university-affiliated ICU. We included patients extubated following successful spontaneous breathing trial (SBT). During the SBT we recorded variables including inspiratory flow. Patients who passed the SBT were extubated onto HFNC. HFNC was titrated from 20 L/min and increased in steps of 10 L/min, up to 60 L/min. At each step, patient's level of comfort was assessed. Fraction of inspired oxygen was titrated to maintain oxygen saturation 92-97%. RESULTS: Nineteen participants were enrolled in the study. There was a significant positive correlation between mean inspiratory flow pre-extubation and the flow setting on HFNC which achieved the best comfort post-extubation (r2 0.88; p < 0.001). Overall, greatest comfort was observed for HFNC flows between 30 and 40 L/min but with individual variability. CONCLUSION: Measuring mean inspiratory flow during an SBT allows for individualised setting of HFNC flow rate immediately post-extubation and achieves the greatest comfort and interface tolerance.

Assessment of Right Ventricular Function With CT and Echocardiography in Patients With Severe Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation.

OBJECTIVES: Changes in right ventricular size and function are frequently observed in patients with severe acute respiratory distress syndrome. The majority of patients who receive venovenous extracorporeal membrane oxygenation undergo chest CT and transthoracic echocardiography. The aims of this study were to compare the use of CT and transthoracic echocardiography to evaluate the right ventricular function and to determine the prevalence of acute cor pulmonale in this patient population. DESIGN: Observational, retrospective, single-center, cohort study. SETTING: Severe respiratory failure and extracorporeal membrane oxygenation center. PATIENTS: About 107 patients with severe acute respiratory distress syndrome managed with venovenous extracorporeal membrane oxygenation. INTERVENTIONS: Chest CT to evaluate right ventricular size and transthoracic echocardiography to evaluate right ventricular size and function. MEASUREMENTS AND MAIN RESULTS: All 107 patients had a qualitative assessment of right ventricular size and function on transthoracic echocardiography. Quantitative measurements were available in 54 patients (50%) who underwent transthoracic echocardiography and in 107 of patients (100%) who received CT. Right ventricular dilatation was defined as a right ventricle end-diastolic diameter greater than left ventricular end-diastolic diameter upon visual assessment or an right ventricle end-diastolic diameter/left ventricular end-diastolic diameter and/or right ventricle cavity area/left ventricular cavity area of greater than 0.9. Right ventricle systolic function was visually estimated as being normal or impaired (visual right ventricular systolic impairment). The right ventricle was found to be dilated in 38/107 patients (36%) and in 58/107 patients (54%), using transthoracic echocardiography or CT right ventricle end-diastolic diameter/left ventricular end-diastolic diameter, respectively. When the CT right ventricle cavity/left ventricular cavity area criterion was used, the right ventricle was dilated in 19/107 patients (18%). About 33/107 patients (31%) exhibited visual right ventricular systolic impairment. Transthoracic echocardiography right ventricle end-diastolic diameter/left ventricular end-diastolic diameter showed good agreement with CT right ventricle cavity/left ventricular cavity area (R 2 = 0.57; p < 0.01). A CT right ventricle cavity/left ventricular cavity area greater than 0.9 provided the optimal cutoff for acute cor pulmonale on transthoracic echocardiography with an AUC of 0.78. Acute cor pulmonale was defined by the presence of a right ventricle "D-shape" and quantitative right ventricle dilatation on transthoracic echocardiography or a right ventricle cavity/left ventricular cavity area greater than 0.9 on CT. A diagnosis of acute cor pulmonale was made in 9/54 (14% patients) on transthoracic echocardiography and in 19/107 (18%) on CT. CONCLUSIONS: Changes in right ventricular size and function are common in patients with severe acute respiratory distress syndrome requiring venovenous extracorporeal membrane oxygenation with up to 18% showing imaging evidence of acute cor pulmonale. A CT right ventricular cavity /left ventricular cavity area greater than 0.9 is indicative of impaired right ventricular systolic function.

Bedside noninvasive monitoring of mechanically ventilated patients.

PURPOSE OF REVIEW: Among noninvasive lung imaging techniques that can be employed at the bedside electrical impedance tomography (EIT) and lung ultrasound (LUS) can provide dynamic, repeatable data on the distribution regional lung ventilation and response to therapeutic manoeuvres.In this review, we will provide an overview on the rationale, basic functioning and most common applications of EIT and Point of Care Ultrasound (PoCUS, mainly but not limited to LUS) in the management of mechanically ventilated patients. RECENT FINDINGS: The use of EIT in clinical practice is supported by several studies demonstrating good correlation between impedance tomography data and other validated methods of assessing lung aeration during mechanical ventilation. Similarly, LUS also correlates with chest computed tomography in assessing lung aeration, its changes and several pathological conditions, with superiority over other techniques. Other PoCUS applications have shown to effectively complement the LUS ultrasound assessment of the mechanically ventilated patient. SUMMARY: Bedside techniques - such as EIT and PoCUS - are becoming standards of the care for mechanically ventilated patients to monitor the changes in lung aeration, ventilation and perfusion in response to treatment and to assess weaning from mechanical ventilation.

A left shift in the oxyhaemoglobin dissociation curve in patients with severe coronavirus disease 2019 (COVID-19).

Critically ill patients with coronavirus disease 2019 (COVID-19) present with hypoxaemia and are mechanically ventilated to support gas exchange. We performed a retrospective, observational study of blood gas analyses (n = 3518) obtained from patients with COVID-19 to investigate changes in haemoglobin oxygen (Hb-O2 ) affinity. Calculated oxygen tension at half-saturation (p50 ) was on average (±SD) 3·3 (3·13) mmHg lower than the normal p50 value (23·4 vs. 26·7 mmHg; P < 0·0001). Compared to an unmatched historic control of patients with other causes of severe respiratory failure, patients with COVID-19 had a significantly higher Hb-O2 affinity (mean [SD] p50 23·4 [3·13] vs. 24·6 [5.4] mmHg; P < 0·0001). We hypothesise that, due to the long disease process, acclimatisation to hypoxaemia could play a role.

Nonantibiotic Pharmacological Treatment of Severe Chronic Obstructive Pulmonary Disease Exacerbations.

Severe, acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a rapid deterioration of the respiratory symptoms of patients with COPD, requiring hospital admission and escalation of pharmacological and nonpharmacological care including the more severe cases of respiratory failure and admission to an intensive care unit (ICU). These events severely impact patients' quality of life and prognosis. This review will describe the nonantibiotic, pharmacological treatment options available for critically ill patients with AECOPD. The aim of treatment is to alleviate symptoms, improve patient's functional and respiratory status, reduce mortality, reduce the risk or the duration of invasive mechanical ventilation, and prevent reexacerbations. Inhaled bronchodilators (i.e., short-acting ß2-agonists and anticholinergics) and systemic corticosteroids are the main drugs used in the treatment of AECOPD. These drugs are also used in the treatment of stable COPD and in the treatment of AECOPD patients in the non-ICU or community setting. Other drugs are essentially only used in the ICU setting such as inhaled anesthetic agents, ketamine, intravenous methylxanthines, and magnesium. Finally, recently developed drugs, such as the specific phosphodiesterase-4 inhibitors, may play a role in the prevention of relapsing AECOPD following a critical event than the treatment of the exacerbation itself. Although they significantly improve the survival of critically ill patients with AECOPD, none of available drugs, alone or combined, is able to significantly modify the prognosis of patients with COPD. This remains an open challenge for the current and future generations of researchers and clinicians.

Prediction of readiness to decannulation from venovenous extracorporeal membrane oxygenation.

OBJECTIVE: The criteria and process for liberation from extracorporeal membrane oxygenation in patients with severe acute respiratory distress syndrome are not standardized. The predictive accuracy of the oxygen challenge test as a diagnostic test in determining weaning and decannulation from venovenous extracorporeal membrane oxygenation was tested. DESIGN: A single-centre, retrospective, observational cohort study. SETTING: Tertiary referral severe respiratory failure centre in a university hospital in the United Kingdom. PATIENTS: 253 adults with severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Patients had median age: 43 years (interquartile range: 32-52) years, extracorporeal membrane oxygenation days: 9 (interquartile range: 6-14) and acute physiology and chronic health evaluation II score 17.5 (interquartile range: 15-20). Oxygen challenge test value (PaO2-OCT) with best prediction was 31 kPa (232 mmHg; sensitivity 0.74; specificity 0.70; area under curve 0.77 (confidence interval: 0.73-0.81)). PaO2-OCT did not perform well as a prospective test to identify readiness to decannulation. Only 24 patients (10%) were decannulated 48 hours after their first positive oxygen challenge test (true positive) and 73.4% patients were false positives (positive oxygen challenge test but not decannulated). True positives had higher tidal volume (541 ± 218 vs 368 mL ± 210; p < 0.05) and minute ventilation (9.34 ± 5.36 vs 6.33 L/min ± 4.43; p < 0.05). Blood flow (3.17 ± 0.23 vs 3.53 L/min ± 0.56; p < 0.05), sweep gas flow (1.42 ±1.83 vs 3.74 L/min ± 2.43; p < 0.05) and extracorporeal membrane oxygenation minute volume at time of first positive oxygen challenge test was lower in true positives (1.66 ± 2.26 vs 4.82 ± 3.43 L/min). This was a strong predictor for decannulation within 48 hours (area under curve: 0.88, confidence interval: 0.88-0.89). CONCLUSIONS: In severe acute respiratory distress syndrome requiring venovenous extracorporeal membrane oxygenation, the PaO2-OCT is a poor predictor of readiness to decannulate from extracorporeal membrane oxygenation. Additional factors involved in the control of respiratory drive and carbon dioxide clearance, particularly native lung dead space and total minute ventilation, should be assessed.

Extracorporeal Membrane Oxygenation for Respiratory Failure.

This review focuses on the use of veno-venous extracorporeal membrane oxygenation for respiratory failure across all blood flow ranges. Starting with a short overview of historical development, aspects of the physiology of gas exchange (i.e., oxygenation and decarboxylation) during extracorporeal circulation are discussed. The mechanisms of phenomena such as recirculation and shunt playing an important role in daily clinical practice are explained.Treatment of refractory and symptomatic hypoxemic respiratory failure (e.g., acute respiratory distress syndrome [ARDS]) currently represents the main indication for high-flow veno-venous-extracorporeal membrane oxygenation. On the other hand, lower-flow extracorporeal carbon dioxide removal might potentially help to avoid or attenuate ventilator-induced lung injury by allowing reduction of the energy load (i.e., driving pressure, mechanical power) transmitted to the lungs during mechanical ventilation or spontaneous ventilation. In the latter context, extracorporeal carbon dioxide removal plays an emerging role in the treatment of chronic obstructive pulmonary disease patients during acute exacerbations. Both applications of extracorporeal lung support raise important ethical considerations, such as likelihood of ultimate futility and end-of-life decision-making. The review concludes with a brief overview of potential technical developments and persistent challenges.

Does Iso-mechanical Power Lead to Iso-lung Damage?: An Experimental Study in a Porcine Model.

BACKGROUND: Excessive tidal volume, respiratory rate, and positive end-expiratory pressure (PEEP) are all potential causes of ventilator-induced lung injury, and all contribute to a single variable: the mechanical power. The authors aimed to determine whether high tidal volume or high respiratory rate or high PEEP at iso-mechanical power produce similar or different ventilator-induced lung injury. METHODS: Three ventilatory strategies-high tidal volume (twice baseline functional residual capacity), high respiratory rate (40 bpm), and high PEEP (25 cm H2O)-were each applied at two levels of mechanical power (15 and 30 J/min) for 48 h in six groups of seven healthy female piglets (weight: 24.2 ± 2.0 kg, mean ± SD). RESULTS: At iso-mechanical power, the high tidal volume groups immediately and sharply increased plateau, driving pressure, stress, and strain, which all further deteriorated with time. In high respiratory rate groups, they changed minimally at the beginning, but steadily increased during the 48 h. In contrast, after a sudden huge increase, they decreased with time in the high PEEP groups. End-experiment specific lung elastance was 6.5 ± 1.7 cm H2O in high tidal volume groups, 10.1 ± 3.9 cm H2O in high respiratory rate groups, and 4.5 ± 0.9 cm H2O in high PEEP groups. Functional residual capacity decreased and extravascular lung water increased similarly in these three categories. Lung weight, wet-to-dry ratio, and histologic scores were similar, regardless of ventilatory strategies and power levels. However, the alveolar edema score was higher in the low power groups. High PEEP had the greatest impact on hemodynamics, leading to increased need for fluids. Adverse events (early mortality and pneumothorax) also occurred more frequently in the high PEEP groups. CONCLUSIONS: Different ventilatory strategies, delivered at iso-power, led to similar anatomical lung injury. The different systemic consequences of high PEEP underline that ventilator-induced lung injury must be evaluated in the context of the whole body.