A 36-Year-Old Woman With Intermittent Cyanosis.

CASE PRESENTATION: A 36-year-old woman with a medical history of opioid use disorder and frequent urinary tract infections presented to the ED from her opioid use disorder clinic, where she was found to have an oxygen saturation by pulse oximetry (Spo2) of 82% on room air. Starting 3 days before presentation, the patient's family noted worsening pale complexion and blue lips at rest. These findings of cyanosis had occurred a few times before and always resolved within a couple days without any medical intervention. She had no pulmonary symptoms outside of long-standing dyspnea with moderate exertion when at work or doing chores around the house. Her medications included methadone 160 mg daily, acetaminophen 650 mg nightly as needed, and phenazopyridine 199 mg three times daily as needed for increased urinary frequency and urethral discomfort that lasted a maximum of 4 days at a time. She confirmed she had started taking a new course of phenazopyridine 4 days before presenting to the ED. She had no dietary restrictions, had been eating her normal diet, and lived in a mobile home with her family, two dogs, and a gerbil. The patient reported using less than 10 tobacco cigarettes per day, one marijuana cigarette nightly, and no alcohol or other drugs. She worked in a warehouse stacking prepackaged bread.

Association of RBC Transfusion Thresholds and Outcomes in Medical Patients With Acute Respiratory Failure Supported With Extracorporeal Membrane Oxygenation: A Single-Center Retrospective Cohort Study.

BACKGROUND: The hemoglobin value to trigger RBC transfusion for patients receiving venovenous extracorporeal membrane oxygenation (ECMO) is controversial. Previous guidelines recommended transfusing to a normal hemoglobin level, but recent studies suggest that more RBC transfusions are associated with increased adverse outcomes. RESEARCH QUESTION: Is implementation of different institutional RBC transfusion thresholds for patients receiving venovenous ECMO associated with changes in RBC use and patient outcomes? STUDY DESIGN AND METHODS: This single-center retrospective study of patients receiving venovenous ECMO used segmented regression to test associations between implementation of institutional transfusion thresholds and trends in RBC use. Associations with secondary outcomes, including in-hospital survival, also were assessed. RESULTS: The study included 229 patients: 91 in the no threshold cohort, 48 in the hemoglobin < 8 g/dL cohort, and 90 in the hemoglobin < 7 g/dL cohort. Despite a decrease in number of RBC units transfused per day of ECMO support after implementation of different thresholds (mean ± SD: 0.6 ± 1.0 in the no threshold cohort, 0.3 ± 0.8 in the hemoglobin < 8 g/dL cohort, and 0.3 ± 1.1 in the hemoglobin < 7 g/dL cohort; P < .001), segmented regression showed no association between implementation of transfusion thresholds and changes in trends in number of RBC units per day of ECMO. We observed an increased hazard of death in the no threshold cohort compared with the hemoglobin < 8 g/dL cohort (adjusted hazard ratio [aHR], 2.08; 95% CI, 1.12-3.88) and in the hemoglobin < 7 g/dL cohort compared with the hemoglobin < 8 g/dL cohort (aHR, 1.93; 95% CI, 1.02-3.62). No difference was found in the hazard of death between the no threshold and hemoglobin < 7 g/dL cohorts (aHR, 1.08; 95% CI, 0.69-1.69). INTERPRETATION: We observed a decrease in number of RBC units per day of ECMO over time, but changes were not associated temporally with implementation of transfusion thresholds. A transfusion threshold of hemoglobin < 8 g/dL was associated with a lower hazard of death, but these findings are limited by study methodology. Further research is needed to investigate optimal RBC transfusion practices for patients supported with venovenous ECMO.

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.

Diagnosis and Epidemiology of Acute Respiratory Failure.

Acute respiratory failure is a common clinical finding caused by insufficient oxygenation (hypoxemia) or ventilation (hypocapnia). Understanding the pathophysiology of acute respiratory failure can help to facilitate recognition, diagnosis, and treatment. The cause of acute respiratory failure can be identified through utilization of physical examination findings, laboratory analysis, and chest imaging.

Ability of the respiratory ECMO survival prediction (RESP) score to predict survival for patients with COVID-19 ARDS and non-COVID-19 ARDS: a single-center retrospective study.

The respiratory ECMO survival prediction (RESP) score is used to predict survival for patients managed with extracorporeal membrane oxygenation (ECMO), but its performance in patients with Coronavirus Disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is unclear. We evaluated the ability of the RESP score to predict survival for patients with both non-COVID 19 ARDS and COVID-19 ARDS managed with ECMO at our institution. Receiver operating characteristic area under the curve (AUC) analysis found the RESP score reasonably predicted survival in patients with non-COVID-19 ARDS (AUC 0.76, 95% CI 0.68-0.83), but not patients with COVID-19 ARDS (AUC 0.54, 95% CI 0.41-0.66).

Mortality in Patients with Obesity and Acute Respiratory Distress Syndrome Receiving Extracorporeal Membrane Oxygenation: The Multicenter ECMObesity Study.

Rationale: Patients with obesity are at increased risk for developing acute respiratory distress syndrome (ARDS). Some centers consider obesity a relative contraindication to receiving extracorporeal membrane oxygenation (ECMO) support, despite growing implementation of ECMO for ARDS in the general population. Objectives: To investigate the association between obesity and mortality in patients with ARDS receiving ECMO. Methods: In this large, international, multicenter, retrospective cohort study, we evaluated the association of obesity, defined as body mass index ⩾ 30 kg/m2, with ICU mortality in patients receiving ECMO for ARDS by performing adjusted multivariable logistic regression and propensity score matching. Measurements and Main Results: Of 790 patients with ARDS receiving ECMO in our study, 320 had obesity. Of those, 24.1% died in the ICU, compared with 35.3% of patients without obesity (P < 0.001). In adjusted models, obesity was associated with lower ICU mortality (odds ratio, 0.63 [95% confidence interval, 0.43-0.93]; P = 0.018). Examined as a continuous variable, higher body mass index was associated with decreased ICU mortality in multivariable regression (odds ratio, 0.97 [95% confidence interval, 0.95-1.00]; P = 0.023). In propensity score matching of 199 patients with obesity to 199 patients without, patients with obesity had a lower probability of ICU death than those without (22.6% vs. 35.2%; P = 0.007). Conclusions: Among patients receiving ECMO for ARDS, those with obesity had lower ICU mortality than patients without obesity in multivariable and propensity score matching analyses. Our findings support the notion that obesity should not be considered a general contraindication to ECMO.

U-Shaped Association Between Carboxyhemoglobin and Mortality in Patients With Acute Respiratory Distress Syndrome on Venovenous Extracorporeal Membrane Oxygenation.

Background: Carbon monoxide (CO) is an endogenous signaling molecule that activates cytoprotective programs implicated in the resolution of acute respiratory distress syndrome (ARDS) and survival of critical illness. Because CO levels can be measured in blood as carboxyhemoglobin, we hypothesized that carboxyhemoglobin percent (COHb%) may associate with mortality. OBJECTIVES: To examine the relationship between COHb% and outcomes in patients with ARDS requiring venovenous extracorporeal membrane oxygenation (ECMO), a condition where elevated COHb% is commonly observed. DESIGN: Retrospective cohort study. SETTING: Academic medical center ICU. PATIENTS: Patients were included that had ARDS on venovenous ECMO. MEASUREMENTS AND MAIN RESULTS: We examined the association between COHb% and mortality using a Cox proportional hazards model. Secondary outcomes including ECMO duration, ventilator weaning, and hospital and ICU length of stay were examined using both subdistribution and causal-specific hazard models for competing risks. We identified 109 consecutive patients for analysis. Mortality significantly decreased per 1 U increase in COHb% below 3.25% (hazard ratio [HR], 0.35; 95% CI, 0.15-0.80; p = 0.013) and increased per 1 U increase above 3.25% (HR, 4.7; 95% CI, 1.5-14.7; p = 0.007) reflecting a nonlinear association (p = 0.006). Each unit increase in COHb% was associated with reduced likelihood of liberation from ECMO and mechanical ventilation, and increased time to hospital and ICU discharge (all p < 0.05). COHb% was significantly associated with hemolysis but not with initiation of hemodialysis or blood transfusions. CONCLUSIONS: In patients with ARDS on venovenous ECMO, COHb% is a novel biomarker for mortality exhibiting a U-shaped pattern. Our findings suggest that too little CO (perhaps due to impaired host signaling) or excess CO (perhaps due to hemolysis) is associated with higher mortality. Patients with low COHb% may exhibit the most benefit from future therapies targeting anti-oxidant and anti-inflammatory pathways such as low-dose inhaled CO gas.

Propofol-Associated Hypertriglyceridemia in Adults With Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation.

The incidence and risk factors for propofol-associated hypertriglyceridemia (HTG) in patients receiving extracorporeal membrane oxygenation (ECMO) have not been evaluated. The purpose of this study was to determine the incidence and risk factors for propofol-associated HTG in patients with acute respiratory distress syndrome (ARDS) on ECMO. This retrospective, cohort study included 167 adults admitted to a medical intensive care unit (ICU) from July 1, 2013 to September 1, 2021, who received 24 hours of concurrent propofol and ECMO therapy. The primary outcome was the incidence of propofol-associated HTG. Secondary outcomes included HTG risk factors, time to development and resolution of HTG, and incidence of pancreatitis. HTG occurred in 58 (34.7%) patients. Patients with HTG had longer durations of ECMO (19 vs. 13 days, p < 0.001), longer ICU length of stay (26.5 vs. 23 days, p = 0.002), and higher in-hospital mortality (51.7 vs. 34.9%, p = 0.047). Baseline sequential organ failure assessment score was associated with an increased risk of developing HTG (hazard ratio [HR] = 1.19, 95% confidence interval [CI] = 1.09-1.30; p < 0.001). Propofol-associated HTG occurred in one-third of patients receiving ECMO for ARDS. Higher baseline illness severity and ECMO duration were associated with an increased risk of propofol-associated HTG.

Extracorporeal Membrane Oxygenation for COVID-19: Comparison of Outcomes to Non-COVID-19-Related Viral Acute Respiratory Distress Syndrome From the Extracorporeal Life Support Organization Registry.

To compare complications and mortality between patients that required extracorporeal membrane oxygenation (ECMO) support for acute respiratory distress syndrome (ARDS) due to COVID-19 and non-COVID-19 viral pathogens. DESIGN: Retrospective observational cohort study. SETTING: Adult patients in the Extracorporeal Life Support Organization registry. PATIENTS: Nine-thousand two-hundred ninety-one patients that required ECMO for viral mediated ARDS between January 2017 and December 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcomes of interest were mortality during ECMO support and prior to hospital discharge. Time-to-event analysis and logistic regression were used to compare outcomes between the groups. Among 9,291 included patients, 1,155 required ECMO for non-COVID-19 viral ARDS and 8,136 required ECMO for ARDS due to COVID-19. Patients with COVID-19 had longer duration of ECMO (19.6 d [interquartile range (IQR), 10.1-34.0 d] vs 10.7 d [IQR, 6.3-19.7 d]; p < 0.001), higher mortality during ECMO support (44.4% vs 27.5%; p < 0.001), and higher in-hospital mortality (50.2% vs 34.5%; p < 0.001). Further, patients with COVID-19 were more likely to experience mechanical and clinical complications (membrane lung failure, pneumothorax, intracranial hemorrhage, and superimposed infection). After adjusting for pre-ECMO disease severity, patients with COVID-19 were more than two times as likely to die in the hospital compared with patients with non-COVID-19 viral ARDS. CONCLUSIONS: Patients with COVID-19 that require ECMO have longer duration of ECMO, more complications, and higher in-hospital mortality compared with patients with non-COVID-19-related viral ARDS. Further study in patients with COVID-19 is critical to identify the patient phenotype most likely to benefit from ECMO and to better define the role of ECMO in the management of this disease process.

Effect of Initial Anticoagulation Targets on Bleeding and Thrombotic Complications for Patients With Acute Respiratory Distress Syndrome Receiving Extracorporeal Membrane Oxygenation.

OBJECTIVE: To evaluate the effect of anticoagulation targets and intensity on bleeding events, thrombotic events, and transfusion requirements in patients with acute respiratory distress syndrome (ARDS) receiving venovenous extracorporeal membrane oxygenation (ECMO) and continuous-infusion heparin. DESIGN: A retrospective cohort study. SETTING: At a single-center, large academic medical center. PARTICIPANTS: One hundred thirty-six critically ill patients. INTERVENTIONS: The following three therapeutic targets were implemented over time and evaluated: (1) no protocol (September 2013-August 2016): no standardized anticoagulation protocol or transfusion thresholds; (2) <50 seconds (September 2016-January 2018): standardized activated partial thromboplastin time (aPTT) goal of <50 seconds, maximum heparin infusion rate of 1,200 units/h, transfusion threshold of hemoglobin (Hgb) <8 g/dL; and (3) 40-to-50 seconds (February 2018-December 2019): aPTT goal of 40-to-50 sec, no maximum heparin infusion rate, transfusion threshold of Hgb <7 g/dL. MEASUREMENTS AND MAIN RESULTS: Continuous variables were compared using the Kruskal-Wallis test, and categorical variables were compared using Fisher exact tests. The primary endpoint, an incidence of at least 1 bleeding event, was highest in the no-protocol group though not statistically different among groups (39.3% v 26.7% v 34%, p = 0.5). Thrombotic complications were similar. The median units of packed red blood cells transfused were highest in the no-protocol group (3 v 2 v 0.5, p < 0.001). CONCLUSION: Anticoagulation protocols standardizing aPTT goals to <50 or 40-to-50 seconds may be a reasonable strategy for patients receiving venovenous ECMO for ARDS. More restrictive hemoglobin transfusion thresholds, in combination with lower aPTT targets, may be associated with a reduction in transfusion requirements.

A Daily, Respiratory Therapist Assessment of Readiness to Liberate From Venovenous Extracorporeal Membrane Oxygenation in Patients With Acute Respiratory Distress Syndrome.

We assessed the effect of implementing a protocol-directed strategy to determine when patients can be liberated from venovenous extracorporeal membrane oxygenation on extracorporeal membrane oxygenation duration, time to initiation of first sweep-off trial, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and survival to hospital discharge. DESIGN: Single-center retrospective before and after study. SETTING: The medical ICU at an academic medical center. PATIENTS: One-hundred eighty patients with acute respiratory distress syndrome managed with venovenous extracorporeal membrane oxygenation at a single institution from 2013 to 2019. INTERVENTIONS: In 2016, our institution implemented a daily assessment of readiness for a trial off extracorporeal membrane oxygenation sweep gas ("sweep-off trial"). When patients met prespecified criteria, the respiratory therapist performed a sweep-off trial to determine readiness for discontinuation of venovenous extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Sixty-seven patients were treated before implementation of the sweep-off trial protocol, and 113 patients were treated after implementation. Patients managed using the sweep-off trial protocol had a significantly shorter extracorporeal membrane oxygenation duration (5.5 d [3-11 d] vs 11 d [7-15.5 d]; p < 0.001), time to first sweep-off trial (2.5 d [1-5 d] vs 7.0 d [5-11 d]; p < 0.001), duration of mechanical ventilation (15.0 d [9-31 d] vs 25 d [21-33 d]; p = 0.017), and ICU length of stay (18 d [10-33 d] vs 27.0 d [21-36 d]; p = 0.008). There were no observed differences in hospital length of stay or survival to hospital discharge. CONCLUSIONS: In patients with acute respiratory distress syndrome managed with venovenous extracorporeal membrane oxygenation at our institution, implementation of a daily, respiratory therapist assessment of readiness for a sweep-off trial was associated with a shorter time to first sweep-off trial and shorter duration of extracorporeal membrane oxygenation. Among survivors, the postassessment group had a reduced duration of mechanical ventilation and ICU lengths of stay. There were no observed differences in hospital length of stay or inhospital mortality.

Monitoring During Mechanical Ventilation.

Mechanical ventilation is an indispensable form of life support for patients undergoing general anesthesia or experiencing respiratory failure in the setting of critical illness. These patients are at risk for a number of complications related to both their underlying disease states and the mechanical ventilation itself. Intensive monitoring is required to identify early signs of clinical worsening and to minimize the risk of iatrogenic harm. Pulse oximetry and capnography are used to ensure that appropriate oxygenation and ventilation are achieved and maintained. Assessments of driving pressure, transpulmonary pressure, and the pressure-volume loop are performed to ensure that adequate PEEP is applied and excess distending pressure is minimized. Finally, monitoring and frequent adjustment of airway cuff pressures is performed to minimize the risk of airway injury and ventilator-associated pneumonia. We will discuss monitoring during mechanical ventilation with a focus on the accuracy, ease of use, and effectiveness in preventing harm for each of these monitoring modalities.

Low Tidal Volumes for Everyone?

Since the first description of mechanical ventilation, our understanding of the positive and negative effects of this form of life support has continued to evolve. To maintain "normal" aeration of the lungs and "normal" blood gas measurements, patients often require much higher airway pressures and tidal volumes than would be expected in a healthy, spontaneously breathing adult. In the early days of mechanical ventilation, the goal was to normalize the blood gas levels, but over the last several decades, we have developed a much better appreciation for the deleterious effects of mechanical ventilation. We have found that lower tidal volumes, which may actually worsen oxygenation and reduce clearance of CO2, can decrease the level of harm caused by mechanical ventilation. This scenario is best described and agreed upon in the setting of ARDS, but a growing body of evidence suggests that the use of higher tidal volumes is harmful in patients with normal lungs undergoing general anesthesia or in patients with lung diseases other than ARDS requiring mechanical ventilation. Finally, the concept of self-induced lung injury has emerged as a mechanism through which patients generating large negative intrathoracic pressures to achieve larger tidal volumes can contribute to worsened lung injury. Given a growing supportive evidence base, we suggest that efforts be made to achieve low tidal volume ventilation in all patients with lung injury or undergoing mechanical ventilation for any reason.

Interhospital ECMO Transport: Regional Focus.

Utilization of extracorporeal membrane oxygenation (ECMO) has increased dramatically over the last decade. Despite this trend, many medical centers have limited, if any, access to this technology or the resources necessary to manage these complex patients. In an effort to improve the current infrastructure of regional ECMO care, ECMO centers of excellence have an obligation to partner with facilities within their communities and regions to increase access to this potentially life-saving technology. While the need for this infrastructure is widely acknowledged in the ECMO community, few reports describe the actual mechanisms by which a successful interfacility transport program can operate. As such, the purpose of this document is to describe the elements of and methods for providing safe and efficient mobile ECMO services from the perspective of an experienced, high-volume tertiary ECMO center of excellence in the Southeastern United States.

A protocol for quantifying cardiogenic oscillations in dynamic 129 Xe gas exchange spectroscopy: The effects of idiopathic pulmonary fibrosis.

The spectral parameters of hyperpolarized 129 Xe exchanging between airspaces, interstitial barrier, and red blood cells (RBCs) are sensitive to pulmonary pathophysiology. This study sought to evaluate whether the dynamics of 129 Xe spectroscopy provide additional insight, with particular focus on quantifying cardiogenic oscillations in the RBC resonance. 129 Xe spectra were dynamically acquired in eight healthy volunteers and nine subjects with idiopathic pulmonary fibrosis (IPF). 129 Xe FIDs were collected every 20 ms (TE  = 0.932 ms, 512 points, dwell time = 32 µs, flip angle ≈ 20°) during a 16 s breathing maneuver. The FIDs were pre-processed using the spectral improvement by Fourier thresholding technique (SIFT) and fit in the time domain to determine the airspace, interstitial barrier, and RBC spectral parameters. The RBC and gas resonances were fit to a Lorentzian lineshape, while the barrier was fit to a Voigt lineshape to account for its greater structural heterogeneity. For each complex resonance the amplitude, chemical shift, linewidth(s), and phase were calculated. The time-averaged spectra confirmed that the RBC to barrier amplitude ratio (RBC:barrier ratio) and RBC chemical shift are both reduced in IPF subjects. Their temporal dynamics showed that all three 129 Xe resonances are affected by the breathing maneuver. Most notably, several RBC spectral parameters exhibited prominent oscillations at the cardiac frequency, and their peak-to-peak variation differed between IPF subjects and healthy volunteers. In the IPF cohort, oscillations were more prominent in the RBC amplitude (16.8 ± 5.2 versus 9.7 ± 2.9%; P = 0.008), chemical shift (0.43 ± 0.33 versus 0.083 ± 0.05 ppm; P < 0.001), and phase (7.7 ± 5.6 versus 1.4 ± 0.8°; P < 0.001). Dynamic 129 Xe spectroscopy is a simple and sensitive tool that probes the temporal variability of gas exchange and may prove useful in discerning the underlying causes of its impairment.