Nuts and bolts of lung ultrasound: utility, scanning techniques, protocols, and findings in common pathologies.

Point of Care ultrasound (POCUS) of the lungs, also known as lung ultrasound (LUS), has emerged as a technique that allows for the diagnosis of many respiratory pathologies with greater accuracy and speed compared to conventional techniques such as chest x-ray and auscultation. The goal of this narrative review is to provide a simple and practical approach to LUS for critical care, pulmonary, and anesthesia providers, as well as respiratory therapists and other health care providers to be able to implement this technique into their clinical practice. In this review, we will discuss the basic physics of LUS, provide a hands-on scanning technique, describe LUS findings seen in normal and pathological conditions (such as mainstem intubation, pneumothorax, atelectasis, pneumonia, aspiration, COPD exacerbation, cardiogenic pulmonary edema, ARDS, and pleural effusion) and also review the training necessary to achieve competence in LUS.

Seized by Blood: A Case of Neurogenic Pulmonary Edema Presenting As Diffuse Alveolar Hemorrhage.

Neurogenic pulmonary edema (NPE) is a condition that is characterized by acute onset respiratory distress that uncommonly can cause diffuse alveolar hemorrhage (DAH). Our case is based on a 41-year-old female with a past medical history of seizure disorder who presented for shortness of breath and hemoptysis after a seizure. A computed tomography (CT) scan of the lungs revealed patchy ground glass subpleural airspace opacities bilaterally with increased secondary pulmonary lobule interstitial thickening. With concerns for DAH, a bronchoscopy was performed and revealed sequentially bloody aliquots. Infectious and autoimmune testing was negative. This case highlights a rare form of DAH arising from NPE.

Prognostic Significance of Lactate Clearance in Cardiogenic Pulmonary Edema in the Emergency Department.

Background and Objectives: Acute cardiorespiratory failure disrupts the delicate balance of energy supply, demand, and consumption, with elevated lactate levels and decreased blood pH serving as crucial indicators. Acute cardiogenic pulmonary edema (ACPO), a common cause of acute respiratory failure, poses a substantial mortality risk. Lactate, a byproduct of pyruvate reduction, is a pertinent marker in perfusion assessment. Lactate clearance (LC) has proven prognostic efficacy in various conditions but lacks consensus on its predictive power in acute cardiogenic pulmonary edema. Materials and Methods: This prospective observational study, conducted in a metropolitan area's third-level emergency department, involved patients with cardiogenic pulmonary edema from May 2021 to August 2023. The inclusion criteria specified acute cardiogenic pulmonary edema, excluding patients with incomplete data or other respiratory conditions. Lactate clearance, calculated at presentation and after 6 h, served as the primary outcome predictor. Our data analysis employed logistic regression, the ROC curve, and statistical tests. Results: The cohort of 106 patients revealed that a lactate clearance below 14.29% was significantly associated with mortality. While 51.6% of survivors were discharged, LC's predictive success for discharge was inconclusive. Logistic regression underscored the significance of lactate clearance, with a one-unit increase yielding a 5.55-fold probability of survival. The AUC for LC was 0.759. Conclusions: This study pioneers the exploration of lactate clearance in patients with acute cardiogenic pulmonary edema. LC below 14.29% signifies a poor prognosis, emphasizing its potential as an early treatment initiation marker. While acknowledging this study's limitations, we advocate for further multicenter research to refine the understanding of lactate clearance in this context.

Negative-Pressure Pulmonary Edema Induced by Flexible Bronchoscopy: A Case Report.

Negative-pressure pulmonary edema (NPPE) arises from excessive inspiratory effort due to upper airway obstruction, often associated with postoperative laryngospasm and upper airway infections like epiglottitis. We present a case of NPPE during bronchoscopy. A 45-year-old female patient, who was undergoing bronchoscopy for interstitial pneumonia evaluation, was examined using a tracheal tube with a 7.5 mm internal diameter and a bronchoscope with a 5.9 mm external diameter. The patient's respiratory condition gradually worsened after intubation. We continued with the examination, supplying approximately 5 L/min of oxygen through the intubation tube. We performed an alveolar lavage, and the recovered fluid gradually turned pale and bloody. After the examination, the patient continued to expectorate pink and frothy sputum and prolonged respiratory failure. Chest radiography revealed new extensive bilateral infiltrates. We ruled out cardiogenic causes through clinical examination, electrocardiogram (ECG), and transthoracic echocardiography. As a result, we suspected that temporary upper airway obstruction during bronchoscopy led to NPPE. Applying continuous positive airway pressure (CPAP) quickly improved the pulmonary edema. The risk of NPPE during bronchoscopy needs to be acknowledged, especially when using larger bronchoscopes and smaller tracheal tubes.

Biophysical properties of alveolar surfactant in drever dogs with hunting associated pulmonary edema.

BACKGROUND: A syndrome of acute non-cardiogenic pulmonary edema associated with hunting is prevalent in the drever breed, but etiology of this syndrome is currently unknown. Alveolar surfactant has a critical role in preventing alveolar collapse and edema formation. The aim of this study was to investigate, whether the predisposition to hunting associated pulmonary edema in drever dogs is associated with impaired biophysical properties of alveolar surfactant. Seven privately owned drever dogs with recurrent hunting associated pulmonary edema and seven healthy control dogs of other breeds were included in the study. All affected dogs underwent thorough clinical examinations including echocardiography, laryngeal evaluation, bronchoscopy, and bronchoalveolar lavage (BAL) as well as head, neck and thoracic computed tomography imaging to rule out other cardiorespiratory diseases potentially causing the clinical signs. Alveolar surfactant was isolated from frozen, cell-free supernatants of BAL fluid and biophysical analysis of the samples was completed using a constrained sessile drop surfactometer. Statistical comparisons over consecutive compression expansion cycles were performed using repeated measures ANOVA and comparisons of single values between groups were analyzed using T-test. RESULTS: There were no significant differences between groups in any of the biophysical outcomes of surfactant analysis. The critical function of surfactant, reducing the surface tension to low values upon compression, was similar between healthy dogs and affected drevers. CONCLUSIONS: The etiology of hunting associated pulmonary edema in drever dogs is not due to an underlying surfactant dysfunction.

Delayed Serotonin Syndrome and Non-cardiogenic Pulmonary Edema Following Bupropion Overdose in a Seven-Year-Old Female: A Case Report and Review of Literature.

Bupropion is an atypical antidepressant prescribed for depression and attention-deficit/hyperactivity disorder and to aid in smoking cessation. Bupropion overdose management is largely aimed toward common sequelae, including seizures, tachycardia, and QTc prolongation. In this case report, we identify a rare event of pediatric bupropion overdose with aforementioned common sequela and atypical features, including a delayed presentation of serotonin syndrome and non-cardiogenic pulmonary edema. This case follows a seven-year-old Caucasian female with autism spectrum disorder (ASD) who presented in status epilepticus following an accidental bupropion overdose and required multiple anti-seizure medications, endotracheal intubation, and admission to the pediatric intensive care unit (PICU). The patient's condition improved, and she was extubated 25 hours after admission and transitioned to high-flow nasal cannula therapy. On day 3 of admission, she became febrile and developed dyspnea with decreased breath sounds and intercostal retractions, tachycardia, a rigid abdomen and extremities with sporadic tremors, pulmonary edema, and a prolonged QTc interval. Targeted therapies were initiated, and following treatment, our patient showed remarkable improvement in the subsequent 24 hours and was discharged home five days after the initial presentation. This case identifies a delayed presentation of uncommon and serious complications of bupropion overdose, including pulmonary edema and serotonin syndrome, in a pediatric patient. Prompt investigation and identification of bupropion toxicity can help practitioners mitigate further complications during admission and reduce morbidity and mortality.

Development of an Automated Ultrasound Signal Indicator of Lung Interstitial Syndrome.

OBJECTIVES: The number and distribution of lung ultrasound (LUS) imaging artifacts termed B-lines correlate with the presence of acute lung disease such as infection, acute respiratory distress syndrome (ARDS), and pulmonary edema. Detection and interpretation of B-lines require dedicated training and is machine and operator-dependent. The goal of this study was to identify radio frequency (RF) signal features associated with B-lines in a cohort of patients with cardiogenic pulmonary edema. A quantitative signal indicator could then be used in a single-element, non-imaging, wearable, automated lung ultrasound sensor (LUSS) for continuous hands-free monitoring of lung fluid. METHODS: In this prospective study a 10-zone LUS exam was performed in 16 participants, including 12 patients admitted with acute cardiogenic pulmonary edema (mean age 60 ± 12 years) and 4 healthy controls (mean age 44 ± 21). Overall,160 individual LUS video clips were recorded. The LUS exams were performed with a phased array probe driven by an open-platform ultrasound system with simultaneous RF signal collection. RF data were analyzed offline for candidate B-line indicators based on signal amplitude, temporal variability, and frequency spectrum; blinded independent review of LUS images for the presence or absence of B-lines served as ground truth. Predictive performance of the signal indicators was determined with receiving operator characteristic (ROC) analysis with k-fold cross-validation. RESULTS: Two RF signal features-temporal variability of signal amplitude at large depths and at the pleural line-were strongly associated with B-line presence. The sensitivity and specificity of a combinatorial indicator were 93.2 and 58.5%, respectively, with cross-validated area under the ROC curve (AUC) of 0.91 (95% CI = 0.80-0.94). CONCLUSION: A combinatorial signal indicator for use with single-element non-imaging LUSS was developed to facilitate continuous monitoring of lung fluid in patients with respiratory illness.

Water Lung: An Interesting Case of Non-cardiogenic Pulmonary Edema in a Heart Failure Patient.

Contrast-induced pulmonary edema is a rare but life-threatening condition often missed in heart failure patients. We present a case of a 65-year-old female with a past medical history of coronary artery disease, diastolic heart failure, and chronic kidney disease who presented with chest pain. She received low osmolar intravenous (IV) contrast for cardiac catheterization. Within 24 hours of receiving the contrast, the patient developed respiratory distress, which was found to be secondary to pulmonary edema. Pulmonary edema was considered to be related to cardiogenic at first; however, the patient's physical examination was normal, with no jugular venous distention (JVD). A transthoracic echocardiogram showed a central venous pressure of 3 mmHg. The patient's respiratory condition improved after receiving an IV diuretic. Chart review showed that the patient had a similar presentation in the past, which was also thought to be related to heart failure leading to recurrent exposure to contrast. Non-cardiogenic pulmonary edema should be considered in the differential diagnosis of pulmonary edema in heart failure patients receiving contrast.

The Burden and Contributing Factors of Cardiogenic Pulmonary Edema Among Acute Heart Failure Patients Admitted to Tertiary Hospital, Eastern Ethiopia.

Background: Despite cardiogenic pulmonary edema is the most common phenotype of acute heart failure (AHF), studies on its burden and associated factors are limited. This study aimed to assess the burden and contributing factors of cardiogenic pulmonary edema in patients with acute heart failure admitted to a tertiary hospital in eastern Ethiopia. Patients and Methods: An institution-based cross-sectional study was conducted on the medical records (n = 276) of patients with AHF between February 01, 2018, and January 31, 2023. A simple random sampling technique was used to select participants from the study population. Bivariable and multivariable logistic regression analyses were used to assess factors associated with the development of cardiogenic pulmonary edema. A P-value ≤0.05 was considered as statistically significant. Results: The prevalence of cardiogenic pulmonary edema was 47.8% in AHF patients. Rural residence (adjusted odds ratio (AOR),9.54), smoking (AOR,3.17), comorbidity (AOR,2.1), and underlying cardiovascular disease (ischemic heart disease, chronic rheumatic valvular heart disease, and hypertensive heart disease with AOR: 6.71, 8.47, and 12.07, respectively) were significantly associated with the development of cardiogenic pulmonary edema in patients with AHF. Conclusion: Nearly half of the patients with AHF had cardiogenic pulmonary edema. Being a rural dweller, cigarette smoking, comorbidities, and underlying cardiac illness were significantly associated with the development of cardiogenic pulmonary edema in patients with AHF.

Cardiogenic Pulmonary Edema in Emergency Medicine.

Cardiogenic pulmonary edema (CPE) is characterized by the development of acute respiratory failure associated with the accumulation of fluid in the lung's alveolar spaces due to an elevated cardiac filling pressure. All cardiac diseases, characterized by an increasing pressure in the left side of the heart, can cause CPE. High capillary pressure for an extended period can also cause barrier disruption, which implies increased permeability and fluid transfer into the alveoli, leading to edema and atelectasis. The breakdown of the alveolar-epithelial barrier is a consequence of multiple factors that include dysregulated inflammation, intense leukocyte infiltration, activation of procoagulant processes, cell death, and mechanical stretch. Reactive oxygen and nitrogen species (RONS) can modify or damage ion channels, such as epithelial sodium channels, which alters fluid balance. Some studies claim that these patients may have higher levels of surfactant protein B in the bloodstream. The correct approach to patients with CPE should include a detailed medical history and a physical examination to evaluate signs and symptoms of CPE as well as potential causes. Second-level diagnostic tests, such as pulmonary ultrasound, natriuretic peptide level, chest radiograph, and echocardiogram, should occur in the meantime. The identification of the specific CPE phenotype is essential to set the most appropriate therapy for these patients. Non-invasive ventilation (NIV) should be considered early in the treatment of this disease. Diuretics and vasodilators are used for pulmonary congestion. Hypoperfusion requires treatment with inotropes and occasionally vasopressors. Patients with persistent symptoms and diuretic resistance might benefit from additional approaches (i.e., beta-agonists and pentoxifylline). This paper reviews the pathophysiology, clinical presentation, and management of CPE.

Effects of MIdazolam versus MOrphine in acute cardiogenic pulmonary edema and chronic obstructive pulmonary disease: An analysis of MIMO trial.

AIMS: Chronic obstructive pulmonary disease (COPD) is an important comorbidity in heart failure. The MIMO trial showed that patients with acute cardiogenic pulmonary edema (ACPE) treated with midazolam had fewer serious adverse events than those treated with morphine. In this post hoc analysis, we examined whether the presence/ absence of COPD modifies the reduced risk of midazolam over morphine. METHODS: Patients >18 years old clinically diagnosed with ACPE and with dyspnea and anxiety were randomized (1:1) at emergency department arrival to receive either intravenous midazolam or morphine. In this post hoc analysis, we calculated the relative risk (RR) of serious adverse events in patients with and without COPD. Calculating the CochranMantel-Haenszel interaction test, we evaluated if COPD modified the reduced risk of serious adverse events in the midazolam arm compared to morphine. RESULTS: Overall, 25 (22.5%) of the 111 patients randomized had a history of COPD. Patients with COPD were more commonly men with a history of previous episodes of heart failure, than participants without COPD. In the COPD group, the RR for the incidence of serious adverse events in the midazolam versus morphine arm was 0.36 (95%CI, 0.1-1.46). In the group without COPD, the RR was 0.44 (95%CI, 0.22-0.91). The presence of COPD did not modify the reduced risk of serious adverse events in the midazolam arm compared to morphine (p for interaction =0.79). CONCLUSIONS: The reduced risk of serious adverse events in the midazolam group compared with morphine is similar in patients with and without COPD.

Acute Decompensated Heart Failure and Cardiogenic Shock Following Propofol Infusion: A Report and Review of Pathophysiology.

Propofol is a widely used general anesthetic agent with a generally familiar and predictable adverse effect profile. Severe left ventricular dysfunction to an ejection fraction of < 35% is a rare adverse effect of propofol, with a scarcity of data in the literature. In this case, we report a 36-year-old female at 36 weeks gestation with a prior remote history of peripartum cardiomyopathy, who, while receiving propofol for general anesthesia during a C-section, developed severe left ventricular dysfunction with an ejection fraction of 20-25%, flash pulmonary edema, and cardiogenic shock. She required initiation of inotropic support and, following weaning of propofol, gradually recovered her ejection fraction over the next 24 hours to 40-45% and to 50-55% at follow-up two weeks after discharge. This case highlights a unique adverse effect of propofol with scarce pre-existing literature and no guidelines on appropriate management. It is essential for clinicians to be familiar with this uncommon complication, particularly as propofol use continues to rise worldwide.

Continuous positive airway pressure ventilation in dogs with acute cardiogenic pulmonary edema is associated with improved clinical parameters and reduced diuretic and oxygen requirements.

OBJECTIVE: To retrospectively compare efficacy of a continuous positive airway pressure (CPAP) helmet against standard oxygen supplementation (STD) administered by nasal cannulae in dogs with acute cardiogenic pulmonary edema (ACPE). ANIMALS: 83 dogs (STD group, n = 41; CPAP group, 42) hospitalized for ACPE (January 2019 to April 2021). METHODS: Mean respiratory rate, heart rate, systolic arterial pressure, and rectal body temperature were compared between and within groups before and at 1 (T1), 2 (T2), 3 (T3), 6 (T6), and 12 (T12) hours from the beginning of STD/CPAP therapy. Duration of oxygen supplementation, hospitalization time, total diuretic dose, additional pharmacological interventions and mortality rates were compared between groups. The veterinary bedside lung ultrasound in emergency score, thoracic radiographs, and arterial blood parameters were compared between and within groups before and at the end of CPAP/STD therapy. RESULTS: Within both groups, clinical parameters decreased during the observation period. Mean respiratory rate and heart rate were significantly lower in the CPAP group than the STD group at T1, T2, T3, T6, and T12. Mean systolic arterial pressure was significantly lower in the CPAP group than the STD group at T2, T3, T6, and T12. Mean oxygen supplementation duration, cumulative loop diuretic dose, and both veterinary bedside lung ultrasound in emergency score and arterial PaCO2 at the end of CPAP/STD therapy were significantly lower in the CPAP group than the STD group. No significant differences were observed in hospitalization time and mortality rates. CLINICAL RELEVANCE: The addition of helmet CPAP compared with standard oxygen administration showed a faster clinical improvement with lower cumulative loop diuretic and shorter oxygen supplementation in dogs hospitalized for ACPE.

The Role of Extracorporeal Membrane Oxygenation Support in Early Management of Unexplained Life-Threatening Acute Heart Failure Due to Left Atrial Cardiac Paraganglioma.

Paragangliomas/pheochromocytomas are uncommon neuroendocrine tumors that arise from chromaffin cells located outside of the adrenal gland. Although cardiac paragangliomas have been observed in all heart chambers, the most prevalent are left-atrial paragangliomas, followed by aortic body tumors. Diagnosis of paragangliomas/pheochromocytomas is mostly achieved with a multimodality approach because of her clinical presentation ranging from incidental findings to refractory acute heart dysfunction. The role of extracorporeal membrane oxygenation support in the early management and diagnosis of unexplained life-threatening cardiogenic shock is rapidly increasing worldwide. However, its clinical utility remains still unclear in intractable heart failure due to primary cardiac paraganglioma. We reported a case of a primary left atrial paraganglioma/pheochromocytoma measuring 34 mm at the maximum diameter in a 58-year-old male patient. The patient presented with acute cardiogenic shock, pulmonary edema, and bilateral stroke. Peripherical mechanical circulatory support, in veno-arterial mode, was rapidly instaured for early management in a life-threatening situation. After normal myocardial function recovery and accurate diagnosis, a surgical approach through aortic and pulmonary artery transection for radical tumor resection and left atrial wall reconstruction was performed. Postprocedural recovery and follow-up at six months were uneventful with excellent neurological recovery.

Pathogenetic role of alveolar surfactant depleted by phosgene: Biophysical mechanisms and peak inhalation exposure metrics.

In contrast to water-soluble respiratory tract irritants in their gas phase, the physicochemical properties of 'hydrophilicity' vs. 'lipophilicity' are the preponderant factors that dictate the site of major retention of the gas at the portal of entry. The lipophilic physical properties of phosgene gas facilitate retention in the alveolar region lined with amphipathic pulmonary surfactant (PS). The relationship between exposure and adverse health outcomes is complex, may vary over time, and is dependent on the biokinetics, biophysics, and pool size of PS relative to the inhaled dose of phosgene. Kinetic PS depletion is hypothesized to occur as inhalation followed by inhaled dose-dependent PS depletion. A kinetic model was developed to better understand the variables characterizing the inhaled dose rates of phosgene vs. PS pool size reconstitution. Modeling and empirical data from published evidence revealed that phosgene gas unequivocally follows a concentration x exposure (C × t) metric, independent of the frequency of exposure. The modeled and empirical data support the hypothesis that the exposure standards of phosgene are described best by a C × t time-averaged metric. Modeled data favorably duplicate expert panel-derived standards. Peak exposures within a reasonable range are of no concern.

Babesiosis: An Atypical Cause of Respiratory Failure.

Babesiosis is a parasitic infection of the Babesia protozoa, which has been increasing in incidence in endemic areas of the United States. Symptoms of babesiosis can occur on a wide spectrum, from a mild flu-like illness to a fulminant disease course. Known complications of severe cases include intravascular hemolytic anemia and may involve the coagulation system, heart, spleen, kidneys, and in some cases, the lungs. This case report describes an 81-year-old, asplenic female in northern Wisconsin who presented to a hospital with shortness of breath and a non-productive cough. Definitive diagnosis of babesiosis, which was made through both a nucleic acid panel and blood smear, was initially delayed given the rare pulmonary manifestation of babesiosis. When the lungs are involved in the disease course, non-cardiogenic pulmonary edema leading to acute respiratory distress syndrome is among the most commonly seen complications. The pathophysiology of pulmonary involvement has not been made entirely clear but is most likely multifactorial, including the sequelae of changes to both the patient's red blood cells and pulmonary vasculature. This report highlights that atypical tick-borne illnesses like babesiosis should be considered as a cause of acute respiratory failure, particularly in the setting of sepsis and fever. The threshold for parasitic testing should be low in patients in endemic regions with risk factors, including increased age and history of asplenia, as babesiosis frequently has no localizing symptoms to suggest a protozoan infection. As babesiosis incidence continues to rise, prompt diagnosis and proper treatment can prevent severe complications and death in patients.

An Internist's Approach to a Case of Negative Pressure Pulmonary Edema: A Rare Cause of Noncardiogenic Pulmonary Edema.

Negative-pressure pulmonary edema (NPPE) is a rare cause of noncardiogenic pulmonary edema, which usually presents postoperatively. Its pathophysiology is mostly described as a profound negative intrathoracic pressure caused by an airway obstruction such as laryngospasm, which may occur during extubation. But, there are other hypotheses about it, such as catecholamines release causing an elevated hydrostatic pressure in the cardiopulmonary circuit and, consequently, a major capillary leak to the interstitium. Its natural course varies, from prompt recovery to intensive care unit escalation and prolonged mechanical ventilation. Although anesthesiologists often detect this condition, this case's objective is to bring awareness of this condition to internists as a potential differential diagnosis for hypoxia in the postoperative setting.

Echocardiographic caudal vena cava measurements in healthy cats and in cats with congestive heart failure and non-cardiac causes of cavitary effusions.

BACKGROUND: Echocardiographic indices of the inferior vena cava have been associated with elevated right atrial pressures in humans. HYPOTHESIS/OBJECTIVES: Describe caudal vena caval (CVC) sonographic dimensions in healthy cats compared to cats with cardiogenic cavitary effusion (CCE), cardiogenic pulmonary edema (CPE), or non-cardiac causes of cavitary effusion (NCE). ANIMALS: 30 healthy control cats and 52 client-owned cats with CCE, CPE, or NCE examined at two university hospitals. METHODS: Sagittal 2-dimensional (2D) and M-mode CVC dimensions were acquired from the subxiphoid view. Caudal vena cava collapsibility index (CVC-CI) was calculated. Variables were compared between study groups using Kruskal-Wallis and Dunn's Bonferroni testing. Receiver operating characteristic curves were used to assess sensitivity and specificity for diagnostic categories. RESULTS: Healthy cats had sagittal 2D and M-mode (median, interquartile range) CVC maximal dimensions of 2.4 mm (1.3-4.0) and 3.4 mm (1.5-4.9) and CVC-CI of 52% (45.2-61.8) and 55% (47.8-61.3), respectively. The CVC maximal dimensions in healthy controls were smaller than in cats with cavitary effusions or pulmonary edema (all P<0.05). CVC-CI was different between CCE and NCE (P<0.0001) with cutoffs of CVC-CI ≤38% (2D) or ≤29% (M-mode) being 90.5% and 85.7% sensitive, and 94.4% and 100% specific for diagnosis of CCE, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Caudal vena cava measurements are larger in cats with cavitary effusions and cats with CPE than healthy cats. In cats with cavitary effusion, decreased CVC-CI, ≤38% (2D) or ≤29% (M-mode), was helpful in distinguishing between cardiogenic and noncardiogenic etiology.

Randomized controlled trial of ultra-protective vs. protective ventilation strategy in veno-arterial extracorporeal membrane oxygenation patients with refractory cardiogenic shock: a study protocol for the ultra-ECMO trial.

Background: A protective or ultra-protective tidal volume strategy is widely applied to patients with acute respiratory distress syndrome (ARDS). The use of very low tidal volume has the potential to further redece ventilation-induced lung injury (VILI) comparde with a "normal" lung protective management. Plus, cardiogenic pulmonary edema (CPE) caused by hydrostatic mechanisms in patients with cardiogenic shock has similar respiratory mechanics to those found in patients with ARDS. And no consensus exists on mechanical ventilation parameter settings in patients with VA-ECMO. The study aimed to investigate the impact of an ultra-protective tidal volume strategy on the 28-day ventilator-free day (VFD) number in VA-ECMO-supported patients with refractory cardiogenic shock, including cardiac arrest. Methods: The Ultra-ECMO trial is a randomized controlled, open-label, single-center prospective superiority trial. At the onset of ECMO initiation, we will divide patients randomly into an intervention group and a control group in a 1:1 ratio. The control group will adopt protective ventilation settings [initial tidal volume: 6 ml/kg of predicted body weight (PBW)] for ventilation, and the intervention group will adopt ultra-protective ventilation settings (initial tidal volume: 4 ml/kg of PBW) for ventilation. The procedure is expected to last 72 h, after which the ventilator settings will be at the intensivists' discretion. The primary outcome is the VFD number at 28 days after inclusion. The secondary outcomes will include respiratory mechanics; analgesic/sedation dosage; lung ultrasound score; interleukin-6, interleukin-8, and monocyte chemotactic protein-1 levels in broncho-alveolar lavage fluid at the moment of enrollment (T0), 24, 48, and 72 h (T1, T2, and T3, respectively) after ECMO initiation; total time (in days) required for ECMO weaning; length of stay in the intensive care unit; total cost of hospitalization; amounts of resuscitative fluids; and in-hospital mortality. Discussion: VA-ECMO-treated patients without ARDS possess abnormal lung function. CPE, thoracic compliance reduction, and poor pulmonary blood perfusion are frequently present, and these patients can more easily progress to ARDS. It seems that targeting the protective tidal volume can lower adverse outcome incidence rates, even in patients without ARDS. This trial seeks to answer the question of whether adopting an ultra-protective tidal volume strategy can lead to superior primary and secondary outcomes compared to adopting a protective tidal volume strategy in patients treated by VA-ECMO. The Ultra-ECMO trial will provide an innovative mechanical ventilation strategy for VA-ECMO-supported patients for improving treatment outcomes at biological and potentially clinical levels. Clinical Trial Registration: ChiCTR2200067118.