Extracorporeal Carbon Dioxide Removal to Avoid Invasive Ventilation During Exacerbations of Chronic Obstructive Pulmonary Disease: VENT-AVOID Trial - A Randomized Clinical Trial.

Rationale: It is unclear whether extracorporeal CO2 removal (ECCO2R) can reduce the rate of intubation or the total time on invasive mechanical ventilation (IMV) in adults experiencing an exacerbation of chronic obstructive pulmonary disease (COPD). Objectives: To determine whether ECCO2R increases the number of ventilator-free days within the first 5 days postrandomization (VFD-5) in exacerbation of COPD in patients who are either failing noninvasive ventilation (NIV) or who are failing to wean from IMV. Methods: This randomized clinical trial was conducted in 41 U.S. institutions (2018-2022) (ClinicalTrials.gov ID: NCT03255057). Subjects were randomized to receive either standard care with venovenous ECCO2R (NIV stratum: n = 26; IMV stratum: n = 32) or standard care alone (NIV stratum: n = 22; IMV stratum: n = 33). Measurements and Main Results: The trial was stopped early because of slow enrollment and enrolled 113 subjects of the planned sample size of 180. There was no significant difference in the median VFD-5 between the arms controlled by strata (P = 0.36). In the NIV stratum, the median VFD-5 for both arms was 5 days (median shift = 0.0; 95% confidence interval [CI]: 0.0-0.0). In the IMV stratum, the median VFD-5 in the standard care and ECCO2R arms were 0.25 and 2 days, respectively; median shift = 0.00 (95% confidence interval: 0.00-1.25). In the NIV stratum, all-cause in-hospital mortality was significantly higher in the ECCO2R arm (22% vs. 0%, P = 0.02) with no difference in the IMV stratum (17% vs. 15%, P = 0.73). Conclusions: In subjects with exacerbation of COPD, the use of ECCO2R compared with standard care did not improve VFD-5. Clinical trial registered with www.clinicaltrials.gov (NCT03255057).

Prevalence and Survival of Prolonged Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: An Analysis of the Extracorporeal Life Support Organization Registry.

OBJECTIVES: To examine trends in utilization and outcomes among patients with the acute respiratory distress syndrome (ARDS) requiring prolonged venovenous extracorporeal membrane oxygenation (VV ECMO) support. DESIGN: Retrospective observational cohort study. SETTING: Adult patients in the Extracorporeal Life Support Organization registry. PATIENTS: Thirteen thousand six hundred eighty-one patients that required ECMO for the support of ARDS between January 2012 and December 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mortality while supported with VV ECMO and survival to hospital discharge based on ECMO duration were examined utilizing multivariable logistic regression. Among the 13,681 patients supported with VV ECMO, 4,040 (29.5%) were supported for greater than or equal to 21 days and 975 (7.1%) for greater than or equal to 50 days. Patients supported with prolonged VV ECMO were less likely to be discharged alive from the hospital compared with those with short duration of support (46.5% vs. 59.7%; p < 0.001). However, among patients supported with VV ECMO greater than or equal to 21 days, duration of extracorporeal life support was not significantly associated with mortality (odds ratio [OR], 0.99; 95% CI, 0.98-1.01; p = 0.87 and adjusted OR, 0.99; 95% CI, 0.97-1.02; p = 0.48). Even in those supported with VV ECMO for at least 120 days (n = 113), 52 (46.0%) of these patients were ultimately discharged alive from the hospital. CONCLUSIONS: Prolonged VV ECMO support of ARDS has increased and accounts for a substantial portion of cases. Among patients that survive for greater than or equal to 21 days while receiving VV ECMO support, duration is not predictive of survival to hospital discharge and clinical recovery may occur even after very prolonged VV ECMO support.

Extracorporeal Carbon Dioxide Removal With the Hemolung in Patients With Acute Respiratory Failure: A Multicenter Retrospective Cohort Study.

OBJECTIVES: Extracorporeal carbon dioxide removal (ECCO 2 R) devices are effective in reducing hypercapnia and mechanical ventilation support but have not been shown to reduce mortality. This may be due to case selection, device performance, familiarity, or the management. The objective of this study is to investigate the effectiveness and safety of a single ECCO 2 R device (Hemolung) in patients with acute respiratory failure and identify variables associated with survival that could help case selection in clinical practice as well as future research. DESIGN: Multicenter, multinational, retrospective review. SETTING: Data from the Hemolung Registry between April 2013 and June 2021, where 57 ICUs contributed deidentified data. PATIENTS: Patients with acute respiratory failure treated with the Hemolung. The characteristics of patients who survived to ICU discharge were compared with those who died. Multivariable logistical regression analysis was used to identify variables associated with ICU survival. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 159 patients included, 65 (41%) survived to ICU discharge. The survival was highest in status asthmaticus (86%), followed by acute respiratory distress syndrome (ARDS) (52%) and COVID-19 ARDS (31%). All patients had a significant reduction in Pa co2 and improvement in pH with reduction in mechanical ventilation support. Patients who died were older, had a lower Pa o2 :F io2 (P/F) and higher use of adjunctive therapies. There was no difference in the complications between patients who survived to those who died. Multivariable regression analysis showed non-COVID-19 ARDS, age less than 65 years, and P/F at initiation of ECCO 2 R to be independently associated with survival to ICU discharge (P/F 100-200 vs <100: odds ratio, 6.57; 95% CI, 2.03-21.33). CONCLUSIONS: Significant improvement in hypercapnic acidosis along with reduction in ventilation supports was noted within 4 hours of initiating ECCO 2 R. Non-COVID-19 ARDS, age, and P/F at commencement of ECCO 2 R were independently associated with survival.

Bayesian methods: a potential path forward for sepsis trials.

BACKGROUND: Given the success of recent platform trials for COVID-19, Bayesian statistical methods have become an option for complex, heterogenous syndromes like sepsis. However, study design will require careful consideration of how statistical power varies using Bayesian methods across different choices for how historical data are incorporated through a prior distribution and how the analysis is ultimately conducted. Our objective with the current analysis is to assess how different uses of historical data through a prior distribution, and type of analysis influence results of a proposed trial that will be analyzed using Bayesian statistical methods. METHODS: We conducted a simulation study incorporating historical data from a published multicenter, randomized clinical trial in the US and Canada of polymyxin B hemadsorption for treatment of endotoxemic septic shock. Historical data come from a 179-patient subgroup of the previous trial of adult critically ill patients with septic shock, multiple organ failure and an endotoxin activity of 0.60-0.89. The trial intervention consisted of two polymyxin B hemoadsorption treatments (2 h each) completed within 24 h of enrollment. RESULTS: In our simulations for a new trial of 150 patients, a range of hypothetical results were observed. Across a range of baseline risks and treatment effects and four ways of including historical data, we demonstrate an increase in power with the use of clinically defensible incorporation of historical data. In one possible trial result, for example, with an observed reduction in risk of mortality from 44 to 37%, the probability of benefit is 96% with a fixed weight of 75% on prior data and 90% with a commensurate (adaptive-weighting) prior; the same data give an 80% probability of benefit if historical data are ignored. CONCLUSIONS: Using Bayesian methods and a biologically justifiable use of historical data in a prior distribution yields a study design with higher power than a conventional design that ignores relevant historical data. Bayesian methods may be a viable option for trials in critical care medicine where beneficial treatments have been elusive.

Technique for circuit exchange in high-risk patients on extracorporeal life support.

Exchanging circuits in patients undergoing extracorporeal life support (ECLS) for component failure can be a life-threatening endeavor if the patient has no native organ function and is fully dependent on ECLS. Traditional circuit exchanges involve replacing the entire circuit at once, leading to a sufficient loss of support that risks hemodynamic deterioration in the absence of mechanical ventilation or mechanical circulatory support. A staged approach is described using a parallel circuit configuration to reduce the risk of physiologic decompensation in patients with total dependence on ECLS. The approach involves splicing in a second primed circuit in parallel, transitioning flow incrementally from old to new circuit, and removing the old circuit. This approach provides hemodynamic and physiologic stability even in patients with absent underlying cardiopulmonary function.

Standardized nomenclature for peripheral percutaneous cannulation of the pulmonary artery in extracorporeal membrane oxygenation: Current uptake and recommendations for improvement.

The rising application of extracorporeal membrane oxygenation (ECMO) has emphasized the need for consistent and standardized terminology, especially concerning peripheral percutaneous cannulation of the pulmonary artery (PPC-PA). The Extracorporeal Life Support Organization (ELSO) Nomenclature Task Force produced the ELSO Maastricht Treaty for extracorporeal life support (ECLS) Nomenclature to address this challenge. However, adherence to nomenclature recommendations has been poor in publications describing PPC-PA. We aim to describe common nomenclature errors and provide a user-guide for abbreviations that can be used by authors, reviewers, and journal staff to ensure properadherence to standardized nomenclature in publications describing PPC-PA.

Dialysis in disaster: Using continuous renal replacement therapy for end-stage renal disease patients, a pilot proof of concept study.

INTRODUCTION: Each dialysis session uses approximately 150 to 200 L of water. The winter storm that swept southwest USA saw an unprecedented disruption of water supplies due to which intermittent hemodialysis could not be performed for end-stage renal disease (ESRD) patients. We present 4 cases when continuous renal replacement therapy (CRRT) was utilized to provide urgent hemodialysis in hemodynamically stable, non-critically ill ESRD patients during this time of water supply crisis. CASE PRESENTATION: Our patients were between the ages 47-62 years old, mostly male. Indications for urgent hemodialysis included volume overload with pulmonary edema and respiratory distress, hypertensive crisis, refractory hyperkalemia, and uremic encephalopathy. The CRRT equipment used included the PRISMAX system for CRRT with M150 filters. Continuous veno-venous hemodialysis (CVVHD) more was used with a dialysate flow rate of 6 L /hour and a blood flow rate of 200/per hour with calculated urea clearance of 100 mL/min. The duration of treatment was 8 h to achieve the target Kt/V of 1.15, comparable to the recommended 1.2 provided by IHD. All patients tolerated the procedure well with the resolution of their acute conditions and normalization of blood pressure and electrolytes. CONCLUSION: We demonstrate limited CRRT as an alternative to safely manage ESRD patients needing urgent hemodialysis in the scenario of a natural disaster resulting in a water outage.

The ELSO Maastricht Treaty for ECLS Nomenclature: abbreviations for cannulation configuration in extracorporeal life support - a position paper of the Extracorporeal Life Support Organization.

BACKGROUND: The Extracorporeal Life Support Organization (ELSO) Maastricht Treaty for Nomenclature in Extracorporeal Life Support (ECLS) established consensus nomenclature and abbreviations for ECLS to ensure accurate, concise communication. METHODS: We build on this consensus nomenclature by layering a framework of precise and efficient abbreviations for cannula configuration that describe flow direction, number of cannulae used, any additional ECLS-related catheters, and cannulation sites. This work is a consensus of international representatives of the ELSO, including those from the North American, Latin American, European, South and West Asian, and Asian-Pacific chapters of ELSO. RESULTS: The classification increases in descriptive capability by introducing a third (cannula tip position) and fourth (cannula dimension) level to those provided in the previous consensus on ECLS cannulation configuration nomenclature. This expansion offers the simplest level needed to convey cannulation information yet allows for more details when required. CONCLUSIONS: A complete nomenclature for ECLS cannulation configurations accommodating future revisions was developed to facilitate ability to compare practices and results, to promote efficient communication, and to improve quality of registry data.

The Extracorporeal Life Support Organization Maastricht Treaty for Nomenclature in Extracorporeal Life Support. A Position Paper of the Extracorporeal Life Support Organization.

Extracorporeal life support (ECLS) was developed more than 50 years ago, initially with venoarterial and subsequently with venovenous configurations. As the technique of ECLS significantly improved and newer skills developed, complexity in terminology and advances in cannula design led to some misunderstanding of and inconsistency in definitions, both in clinical practice and in scientific research. This document is a consensus of multispecialty international representatives of the Extracorporeal Life Support Organization, including the North America, Latin America, EuroELSO, South West Asia and Africa, and Asia-Pacific chapters, imparting a global perspective on ECLS. The goal is to provide a consistent and unambiguous nomenclature for ECLS and to overcome the inconsistent use of abbreviations for ECLS cannulation. Secondary benefits are ease of multicenter collaboration in research, improved registry data quality, and clear communication among practitioners and researchers in the field.

Pre-operative core muscle index in combination with hypoalbuminemia is associated with poor prognosis in advanced ovarian cancer.

BACKGROUND AND OBJECTIVES: Age and frailty have been correlated with poor clinical outcomes in cancer. Core muscle index (CMI) and nutritional status are integral in assessing frailty. We explored the effect of pre-operative serum albumin and body composition on clinical outcomes in patients with epithelial ovarian cancer (EOC). METHODS: We identified stage III-IV EOC patients undergoing primary cytoreductive surgery from 2007 to 2015. Data were abstracted from medical records. Body composition measurements were obtained from pre-operative imaging. Psoas muscle cross-sectional area was normalized to height2 to determine CMI. Sarcopenia was defined as CMI below the population mean. The influence of sarcopenia on short-term morbidity was evaluated. Relationships among body composition measurements and albumin were assessed with Spearman correlations. Patient characteristics and body composition measurements between patients with and without sarcopenia were compared with parametric and non-parametric statistical methods. Kaplan-Meier survival curves were compared using log-rank. RESULTS: 102 women met inclusion criteria. Sarcopenia correlated with albumin (P = 0.0002). Sarcopenia was not associated with short-term morbidity or time to recurrence. Sarcopenia was associated with nearly a fourfold increased risk of death when hypoalbuminemia was present (P = 0.02). CONCLUSIONS: Pre-operative sarcopenia in combination with hypoalbuminemia was associated with significantly worse survival.

Factors influencing primary treatment of midline vulvar cancers.

OBJECTIVES: Advanced vulvar cancers involving midline structures pose a therapeutic challenge. Our objectives were to review the management and outcomes, and identify factors influencing primary treatment modality. METHODS: Patients with midline vulvar cancers diagnosed from 1985 to 2012 were included in the analysis. Medical records were abstracted for demographics, clinico-pathological findings, treatment, and outcomes. Groin node status was defined by clinical findings or pathology. Survival was analyzed by Kaplan-Meier method and differences by log-rank test and Cox proportional hazards model. Factors influencing treatment modality were evaluated using stepwise logistic regression. RESULTS: Forty-two patients were identified. Twenty-one underwent primary radical vulvectomy and 21 underwent primary radiation. Median tumor diameter was 3.4cm (range 2-9cm) for primary radical vulvectomy and 5cm (range 2.3-15cm) for primary radiation. Primary radiation was significantly associated with a tumor diameter ≥5cm (p=0.02), or when 2 or more midline (p=0.008) or 1 or more mucosal structures (p=0.03) were involved. On multivariate analysis, age and tumor diameter were predictors of progression-free survival (PFS) (p=0.02 and p=0.0004, respectively) and overall survival (OS) (p=0.03 and p=0.0005, respectively). Thirty-month OS for primary surgery and primary radiation was 74% and 71% (p=0.78), respectively. There were no differences in PFS or recurrence rates between the two treatment groups. CONCLUSIONS: Clinical tumor diameter and the number of midline or mucosal structures involved influence selection of primary treatment modality. Survival outcomes and recurrence rates did not differ between treatment groups. Age and tumor diameter are important prognostic factors for survival.

Percutaneous cannulation for extracorporeal membrane oxygenation by intensivists: a retrospective single-institution case series.

OBJECTIVE: Extracorporeal membrane oxygenation provides support for patients with severe acute cardiopulmonary failure, allowing the application of lung or myocardial rest in anticipation of organ recovery, or as a bridge to long-term support. Advances in technology have improved the safety and ease of application of extracorporeal membrane oxygenation. Percutaneous cannulation is one of these advances and is now preferred over surgical cannulation in most cases. Percutaneous cannulation is increasingly performed by intensivists, cardiologists, interventional radiologists, and related specialties. The objective of this study is to review the experience of percutaneous cannulation by intensivists at a single institution. DESIGN: A retrospective review of 100 subjects undergoing percutaneous cannulation for extracorporeal membrane oxygenation. SETTING: Adult ICUs and PICUs at a tertiary academic medical institution. PATIENTS: Critically ill neonatal, pediatric, and adult subjects with severe respiratory and/or cardiac failure undergoing percutaneous cannulation for extracorporeal membrane oxygenation. Modes of support included venoarterial, venovenous, venovenoarterial, and arteriovenous. INTERVENTIONS: Percutaneous extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Case reports submitted to the Extracorporeal Life Support Organization and hospital records of the subjects were retrospectively reviewed. Subject demographics, type of support, cannulation configuration, types of cannulas, use of imaging modalities, and complications were recorded and summarized. One hundred ninety cannulations with cannula sizes from size 12 to 31F were performed by four intensivists in 100 subjects. Twenty-three were arterial (12-16F) and 167 were venous (12-31F). Preinsertion ultrasound was performed in 93 subjects (93%), fluoroscopic guidance in 79 subjects (85% of nonarteriovenous subjects), and ultrasound-guided insertion was performed in 65 subjects (65%). Two major complications occurred, each associated with mortality. Cannulation was successful in all other subjects (98% of subjects and 99% of cannulations). There were no cases of cannula-related bloodstream infection. CONCLUSIONS: Percutaneous cannulation for extracorporeal membrane oxygenation by intensivists can be performed with a high rate of success and a low rate of complications when accompanied by imaging support.

Pathophysiology and Prevention of Manual-Ventilation-Induced Lung Injury (MVILI).

Manual ventilation, most commonly with a bag-valve mask, is a form of short-term ventilation used during resuscitative efforts in emergent and out-of-hospital scenarios. However, compared to mechanical ventilation, manual ventilation is an operator-dependent skill that is less well controlled and is highly subject to providing inappropriate ventilation to the patient. This article first reviews recent manual ventilation guidelines set forth by the American Heart Association and European Resuscitation Council for providing appropriate manual ventilation parameters (e.g., tidal volume and respiratory rate) in different patient populations in the setting of cardiopulmonary resuscitation. There is then a brief review of clinical and manikin-based studies that demonstrate healthcare providers routinely hyperventilate patients during manual ventilation, particularly in emergent scenarios. A discussion of the possible mechanisms of injury that can occur during inappropriate manual hyperventilation follows, including adverse hemodynamic alterations and lung injury such as acute barotrauma, gastric regurgitation and aspiration, and the possibility of a subacute, inflammatory-driven lung injury. Together, these injurious processes are described as manual-ventilation-induced lung injury (MVILI). This review concludes with a discussion that highlights recent progress in techniques and technologies for minimizing manual hyperventilation and MVILI, with a particular emphasis on tidal-volume feedback devices.

Central Venopulmonary Extracorporeal Membrane Oxygenation: Background and Standardized Nomenclature.

This review highlights advancements in extracorporeal life support (ECLS), emphasizing the critical role of standardized terminology, particularly for extracorporeal membrane oxygenation (ECMO) in treating right ventricular and respiratory failure. Advocating for the adoption of the Extracorporeal Life Support Organization (ELSO) Maastricht Treaty for ECLS Nomenclature guidelines, it aims to resolve communication barriers in the ECMO field. Focusing on venopulmonary (VP) ECMO utilizing central pulmonary artery (PA) access, this review details surgical approaches and introduces a terminology guide to support effective knowledge exchange and advancements in patient care.

Extracorporeal Carbon Dioxide Removal With the Hemolung in Patients With Acute-on-Chronic Respiratory Failure: A Multicenter Retrospective Cohort Study.

Extracorporeal carbon dioxide removal (ECCO2R) devices are increasingly used in treating acute-on-chronic respiratory failure caused by chronic lung diseases. There are no large studies that investigated safety, efficacy, and the independent association of prognostic variables to survival that could define the role of ECCO2R devices in such patients. This multicenter, multinational, retrospective study investigated the efficacy, safety of a single ECCO2R device (Hemolung) in patients with acute on chronic respiratory failure and identified variables independently associated with intensive care unit (ICU) survival. The primary outcome was improvement in blood gasses with the use of Hemolung. Secondary outcomes included reduction in tidal volume, respiratory rate, minute ventilation, survival to ICU discharge, and complication profile. Multivariable regression analysis was used to identify variables that are independently associated with ICU survival. A total of 62 patients were included. There was a significant improvement in pH and partial pressure of carbon dioxide in arterial blood (PaCO2) along with a reduction in respiratory rate, tidal volume, and minute ventilation with Hemolung therapy. The complication profile did not differ between survivors and nonsurvivors. Multivariable analysis identified the duration of Hemolung therapy to be independently associated with survival to ICU discharge (adjusted odds ratio = 1.21; 95% confidence interval [CI] = 1.040-1.518; p = 0.01).

The ReInvigorate Study-phrenic nerve-to-diaphragm stimulation for weaning from mechanical ventilation: a protocol for a randomized pivotal clinical trial.

BACKGROUND: In the United States in 2017, there were an estimated 903,745 hospitalizations involving mechanical ventilation (MV). Complications from ventilation can result in longer hospital stays, increased risk of disability, and increased healthcare costs. It has been hypothesized that electrically pacing the diaphragm by phrenic nerve stimulation during mechanical ventilation may minimize or reverse diaphragm dysfunction, resulting in faster weaning. METHODS: The ReInvigorate Trial is a prospective, multicenter, randomized, controlled clinical trial evaluating the safety and efficacy of Stimdia's pdSTIM System for facilitating weaning from MV. The pdSTIM system employs percutaneously placed multipolar electrodes to stimulate the cervical phrenic nerves and activate contraction of the diaphragm bilaterally. Patients who were on mechanical ventilation for at least 96 h and who failed at least one weaning attempt were considered for enrollment in the study. The primary efficacy endpoint was the time to successful liberation from mechanical ventilation (treatment vs. control). Secondary endpoints will include the rapid shallow breathing index and other physiological and system characteristics. Safety will be summarized for both primary and additional analyses. All endpoints will be evaluated at 30 days or at the time of removal of mechanical ventilation, whichever is first. DISCUSSION: This pivotal study is being conducted under an investigational device exception with the U.S. Food and Drug Administration. The technology being studied could provide a first-of-kind therapy for difficult-to-wean patients on mechanical ventilation in an intensive care unit setting. TRIAL REGISTRATION: Clinicaltrials.gov, NCT05998018 , registered August 2023.