Virtual Procedural Supervision During the COVID-19 Pandemic: A Novel Pilot for Supervising Invasive Bedside Procedures in the ICU.

The ability to perform invasive bedside procedures (IBPs) safely and efficiently is a core skill set within critical care medicine. Fellowship training provides a pivotal time for learners to attain baseline proficiency in such procedures to decrease patient complications. The coronavirus disease 2019 pandemic has posed distinct challenges to the traditional model of teaching and supervising IBPs in the intensive care unit, including stewardship of personal protective equipment and limiting health care worker exposure to persons with coronavirus disease 2019. To address these challenges, we piloted a novel method of IBP supervision and teaching using a virtual monitoring system. In this virtual procedural supervision model, the supervising teacher is located outside the patient room, limiting personal protective equipment use and health care worker exposure. An audiovisual monitoring system allowed communication between the teacher and the learner as well as supervisor visualization of the procedural encounter. Virtual supervision was used for central line placement and bronchoscopy in the medical intensive care unit with no complications or instances of the supervisor needing to enter the patient room. Success was felt to depend on camera positioning and preprocedure planning and to be best for advanced learners who would not require tactile feedback. Upper level learners appreciated autonomy granted by this process. Virtual IBP supervision is felt to be a useful tool in specific situations. As with any tool, there are notable strengths and limitations. Success is felt to be optimized when attention is paid to procedural teaching best practices, learner selection, and technological logistics.

Etiology, incidence, and outcomes of patient-ventilator asynchrony in critically-ill patients undergoing invasive mechanical ventilation.

Patient-ventilator asynchrony (PVA) is commonly encountered during mechanical ventilation of critically ill patients. Estimates of PVA incidence vary widely. Type, risk factors, and consequences of PVA remain unclear. We aimed to measure the incidence and identify types of PVA, characterize risk factors for development, and explore the relationship between PVA and outcome among critically ill, mechanically ventilated adult patients admitted to medical, surgical, and medical-surgical intensive care units in a large academic institution staffed with varying provider training background. A single center, retrospective cohort study of all adult critically ill patients undergoing invasive mechanical ventilation for ≥ 12 h. A total of 676 patients who underwent 696 episodes of mechanical ventilation were included. Overall PVA occurred in 170 (24%) episodes. Double triggering 92(13%) was most common, followed by flow starvation 73(10%). A history of smoking, and pneumonia, sepsis, or ARDS were risk factors for overall PVA and double triggering (all P < 0.05). Compared with volume targeted ventilation, pressure targeted ventilation decreased the occurrence of events (all P < 0.01). During volume controlled synchronized intermittent mandatory ventilation and pressure targeted ventilation, ventilator settings were associated with the incidence of overall PVA. The number of overall PVA, as well as double triggering and flow starvation specifically, were associated with worse outcomes and fewer hospital-free days (all P < 0.01). Double triggering and flow starvation are the most common PVA among critically ill, mechanically ventilated patients. Overall incidence as well as double triggering and flow starvation PVA specifically, portend worse outcome.

The Impact of a Standardized Refractory Hypoxemia Protocol on Outcome of Subjects Receiving Venovenous Extracorporeal Membrane Oxygenation.

BACKGROUND: Current mechanical ventilation practice and the use of treatment adjuncts in patients requiring extracorporeal membrane oxygenation (ECMO) for refractory hypoxemia (RH) vary widely and their impact on outcomes remains unclear. In 2015, we implemented a standardized approach to protocolized ventilator settings and guide the escalation of adjunct therapies in patients with RH. This study aimed to investigate ICU mortality, its associated risk factors, and mechanical ventilation practice before and after the implementation of a standardized RH guideline in patients requiring venovenous ECMO (VV-ECMO). METHODS: This was a single-center, retrospective cohort study of patients undergoing VV-ECMO due to RH respiratory failure between January 2008 and March 2015 (before RH protocol implementation) and between April 2015 and October 2019 (after RH protocol implementation). RESULTS: A total of 103 subjects receiving VV-ECMO for RH were analyzed. After implementation of the RH protocol, more subjects received prone positioning (6.7% vs 23.3%, P = .02), and fewer received high-frequency oscillatory ventilation than before launching the RH protocol (0% vs 13.3%, P = .01). Plateau pressure was also lower before initiation of ECMO (P = .04) and at day 1 during ECMO (P = .045). Driving pressure was consistently lower at days 1, 2, and 3 after ECMO initiation: median 13.0 (interquartile range [IQR] 10.6-18.0) vs 16.0 (IQR 14.0-20.0) cm H2O at day 1 (P = .003); 13.0 (IQR 11.0-15.9) vs 15.5 (IQR 12.0-20.0) cm H2O at day 2 (P = .03); and 12.0 (IQR 10.0-14.5) vs 15.0 (IQR 12.0-19.0) cm H2O at day 3 (P = .005). CONCLUSIONS: The implementation of a standardized RH guideline improved compliance with a lung-protective ventilation strategy and utilization of the prone position and was associated with lower driving pressure during the first 3 days after ECMO initiation in subjects with refractory hypoxemia.

Outcomes of COVID-19 With the Mayo Clinic Model of Care and Research.

OBJECTIVE: To report the Mayo Clinic experience with coronavirus disease 2019 (COVID-19) related to patient outcomes. METHODS: We conducted a retrospective chart review of patients with COVID-19 diagnosed between March 1, 2020, and July 31, 2020, at any of the Mayo Clinic sites. We abstracted pertinent comorbid conditions such as age, sex, body mass index, Charlson Comorbidity Index variables, and treatments received. Factors associated with hospitalization and mortality were assessed in univariate and multivariate models. RESULTS: A total of 7891 patients with confirmed COVID-19 infection with research authorization on file received care across the Mayo Clinic sites during the study period. Of these, 7217 patients were adults 18 years or older who were analyzed further. A total of 897 (11.4%) patients required hospitalization, and 354 (4.9%) received care in the intensive care unit (ICU). All hospitalized patients were reviewed by a COVID-19 Treatment Review Panel, and 77.5% (695 of 897) of inpatients received a COVID-19-directed therapy. Overall mortality was 1.2% (94 of 7891), with 7.1% (64 of 897) mortality in hospitalized patients and 11.3% (40 of 354) in patients requiring ICU care. CONCLUSION: Mayo Clinic outcomes of patients with COVID-19 infection in the ICU, hospital, and community compare favorably with those reported nationally. This likely reflects the impact of interprofessional multidisciplinary team evaluation, effective leveraging of clinical trials and available treatments, deployment of remote monitoring tools, and maintenance of adequate operating capacity to not require surge adjustments. These best practices can help guide other health care systems with the continuing response to the COVID-19 pandemic.

Updated guidance on the management of COVID-19: from an American Thoracic Society/European Respiratory Society coordinated International Task Force (29 July 2020).

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research. METHODS: An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion. RESULTS: The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3 months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder. CONCLUSIONS: The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities.

The Clinical Effect of an Early, Protocolized Approach to Mechanical Ventilation for Severe and Refractory Hypoxemia.

BACKGROUND: ARDS remains a source of significant morbidity and mortality in the critically ill patient. The mainstay of therapy entails invasive mechanical ventilation utilizing a lung-protective strategy designed to limit lung injury associated with excessive stress and strain while the underlying etiology of respiratory failure is identified and treated. Less is understood about what to do once conventional ventilation parameters have been optimized but the patient's respiratory status remains unchanged or worsens. In 2015, a protocolized, stepwise approach to mechanical ventilation with partially automated and clearly defined thresholds for management changes was implemented at our institution. We hypothesized that, by identifying appropriate patients earlier, time-to-escalation and rescue therapy implementation would be shortened. METHODS: Subjects with severe ARDS, treated with prone positioning based on our institution's protocolized approach from December 2013 to August 2016 were included. Their baseline characteristics, severity of illness scores, and mechanical ventilation parameters were collected and analyzed. RESULTS: Baseline characteristics, tidal volumes, PaO2 /FIO2 , duration of ventilation after proning, and mortality were similar in both groups. Median (interquartile range [IQR]) PEEP at the time of proning was higher after the protocol implementation (12.5 cm H2O [IQR 6.5-19.4] vs 18 cm H2O [IQR 10-22], P = .386), and mean (IQR) respiratory system driving pressure was lower (16 cm H2O [IQR 13-36.2] vs 12 cm H2O [IQR 9-19.6], P = .029). Median (IQR) time from refractory hypoxemia identification to proning was shorter after protocol implementation (42.2 h [IQR 6.83-347.2] vs 16.3 h [IQR 1-99.7], I = .02), and PaO2 /FIO2 at 1 h after proning was higher. ICU and hospital LOS were shorter after the protocol implementation. CONCLUSIONS: Following the implementation of an early, evidence-based, protocolized approach to optimizing mechanical ventilation, subjects with true refractory hypoxemia were identified earlier and time to proning was significantly shorter. Despite improvement in the evaluation and management of refractory hypoxemia as well as time to initiation of prone positioning, mortality was unchanged and there was variation in the duration of the position.

Ketamine/propofol admixture vs etomidate for intubation in the critically ill: KEEP PACE Randomized clinical trial.

BACKGROUND: Periintubation hypotension is associated with poor outcomes in the critically ill. We aimed to determine if an admixture of ketamine and propofol for emergent endotracheal intubation in critically ill patients was superior to etomidate. Primary endpoint was the change in mean arterial pressure from baseline to 5 minutes postdrug administration. METHODS: Emergent-use, stratified (shock status and unit type), multiunit, randomized, parallel-group superiority clinical trial was conducted at a tertiary academic medical center. Adult medical/surgical and transplant/oncologic intensive care unit patients undergoing emergent intubation were assigned randomly to receive either ketamine/propofol admixture (0.5 mg/kg of ketamine and propofol each) or reduced dose etomidate (0.15 mg/kg) for emergent intubation. RESULTS: One hundred sixty participants were randomized, and 152 (79 ketamine/propofol admixture, 73 etomidate) were included in the intention-to-treat analysis. There was no statistically significant difference in mean arterial pressure change from baseline to 5 minutes postdrug administration (treatment difference [ketamine/propofol admixture-etomidate]: -2.1 mm Hg; 95% confidence interval, -6.9 mm Hg to +2.7 mm Hg; p = 0.385). In addition, no statistically significant difference was demonstrated in the change of mean arterial pressure from baseline at 10 minutes and 15 minutes postdrug administration, no statistical difference in the use of new-onset vasoactive agents or difficulty of intubation between groups. More patients in the etomidate group required non-red blood cell transfusions (16 [22%] vs. 8 [10%], p = 0.046). For patients who had adrenal testing performed, more patients in the etomidate group developed immediate adrenal insufficiency (13 [81%] of 16 vs. 5 [38%] of 13, p = 0.027). Serious adverse events were rare, 2 (3%) (cardiac arrest, hypotension) in ketamine/propofol admixture and 4 (5%) (hypertension, hypotension) in etomidate (p = 0.430). CONCLUSION: In a heterogeneous critically ill population, ketamine/propofol admixture was not superior to a reduced dose of etomidate at preserving per-intubation hemodynamics and appears to be a safe alternative induction agent in the critically ill. LEVEL OF EVIDENCE: Therapeutic/Care Management, level II. TRIAL REGISTRY: ClinicalTrials.gov, NCT02105415, Ketamine/Propofol Admixture "Ketofol" at Induction in the Critically Ill Against Etomidate: KEEP PACE Trial, IRB 13-000506, Trial Registration: March 31, 2014.

Hypercapnia Alters Alveolar Epithelial Repair by a pH-Dependent and Adenylate Cyclase-Mediated Mechanism.

Lung cell injury and repair is a hallmark of the acute respiratory distress syndrome (ARDS). Lung protective mechanical ventilation strategies in these patients may lead to hypercapnia (HC). Although HC has been explored in the clinical context of ARDS, its effect upon alveolar epithelial cell (AEC) wounding and repair remains poorly understood. We have previously reported that HC alters the likelihood of AEC repair by a pH-sensitive but otherwise unknown mechanism. Adenylate cyclase (AC) is an attractive candidate as a putative AEC CO2 sensor and effector as it is bicarbonate sensitive and controls key mediators of AEC repair. The effect of HC on AC activity and plasma membrane (PM) wound repair was measured in AEC type 1 exposed to normocapnia (NC, 40 Torr) or HC (80 Torr), ± tromethamine (THAM) or sodium bicarbonate (HCO3) ± AC probes in a micropuncture model of AEC injury relevant to ARDS. Intracellular pH and AC activity were measured and correlated with repair. HC decreased intracellular pH 0.56, cAMP by 37%, and absolute PM repair rate by 26%. Buffering or pharmacologic manipulation of AC reduced or reversed the effects of HC on AC activity (THAM 103%, HCO3 113% of NC cAMP, ns; Forskolin 168%, p < 0.05) and PM repair (THAM 87%, HCO3 108% of NC likelihood to repair, ns; Forskolin 160%, p < 0.01). These findings suggest AC to be a putative AEC CO2 sensor and modulator of AEC repair, and may have implications for future pharmacologic targeting of downstream messengers of the AC-cAMP axis in experimental models of ARDS.

Physiology-guided management of hemodynamics in acute respiratory distress syndrome.

Skillfully implemented mechanical ventilation (MV) may prove of immense benefit in restoring physiologic homeostasis. However, since hemodynamic instability is a primary factor influencing mortality in acute respiratory distress syndrome (ARDS), clinicians should be vigilant regarding the potentially deleterious effects of MV on right ventricular (RV) function and pulmonary vascular mechanics (PVM). During both spontaneous and positive pressure MV (PPMV), tidal changes in pleural pressure (PPL), transpulmonary pressure (PTP, the difference between alveolar pressure and PPL), and lung volume influence key components of hemodynamics: preload, afterload, heart rate, and myocardial contractility. Acute cor pulmonale (ACP), which occurs in 20-25% of ARDS cases, emerges from negative effects of lung pathology and inappropriate changes in PPL and PTP on the pulmonary microcirculation during PPMV. Functional, minimally invasive hemodynamic monitoring for tracking cardiac performance and output adequacy is integral to effective care. In this review we describe a physiology-based approach to the management of hemodynamics in the setting of ARDS: avoiding excessive cardiac demand, regulating fluid balance, optimizing heart rate, and keeping focus on the pulmonary circuit as cornerstones of effective hemodynamic management for patients in all forms of respiratory failure.

Positional effects on the distributions of ventilation and end-expiratory gas volume in the asymmetric chest-a quantitative lung computed tomographic analysis.

BACKGROUND: Body positioning affects the configuration and dynamic properties of the chest wall and therefore may influence decisions made to increase or decrease ventilating pressures and tidal volume. We hypothesized that unlike global functional residual capacity (FRC), component sector gas volumes and their corresponding regional tidal expansions would vary markedly in the setting of unilateral pleural effusion (PLEF), owing to shifting distributions of aeration and collapse as posture changed. METHODS: Six deeply anesthetized swine underwent tracheostomy, thoracostomy, and experimental PLEF with 10 mL/kg of radiopaque isotonic fluid randomly instilled into either pleural space. Animals were ventilated at VT = 10 mL/kg, frequency = 15 bpm, I/E = 1:2, PEEP = 1 cmH2O, and FiO2 = 0.5. Quantitative lung computed tomographic (CT) analysis of regional aeration and global FRC measurements by nitrogen wash-in/wash-out technique was performed in each of these randomly applied positions: semi-Fowler's (inclined 30° from horizontal in the sagittal plane); prone, supine, and lateral positions with dependent PLEF and non-dependent PLEF. RESULTS: No significant differences in total FRC were observed among the horizontal positions, either at baseline (p = 0.9037) or with PLEF (p = 0.58). However, component sector total gas volumes in each phase of the tidal cycle were different within all studied positions with and without PLEF (p = < .01). Compared to other positions, prone and lateral positions with non-dependent PLEF had more homogenous VT distributions among quadrants (p = .051). Supine position was associated with most dependent collapse and greatest tendency for tidal recruitment (48 vs ~ 22%, p = 0.0073). CONCLUSIONS: Changes in body position in the setting of effusion-caused chest asymmetry markedly affected the internal distributions of gas volume, collapse, ventilation, and tidal recruitment, even though global FRC measurements provided little indication of these potentially important positional changes.

Expanding the Presence of Primary Services at Rapid Response Team Activations: A Quality Improvement Project.

Rapid response teams (RRTs) were implemented to provide critical care services for deteriorating patients outside of intensive care units. To date, research on RRT has been conflicting, with some studies showing significant mortality benefit and reduction in cardiac arrest events and others showing no benefit. However, studies have consistently showed improved outcomes when RRTs work closely with primary services. Baseline data analysis at our institution found that primary services were present only on 50% of RRT activations. This quality improvement project aimed to improve the presence of primary services during RRT activations by 25%. With a survey, the main barrier that prevented primary services to be present was identified as the primary services' failure to recognize them as a crucial part of the RRT. Education tools and in-person sessions were implemented reinforcing the importance of primary services presence during RRT activations. The intervention leads to increasing presence of primary services at RRT activations, transfers to higher level of care, and changes in code status. However, there was no difference in hospital or intensive care unit length of stay or in survival.

Mechanosensitive ion channel Piezo2 is important for enterochromaffin cell response to mechanical forces.

KEY POINTS: The gastrointestinal epithelial enterochromaffin (EC) cell synthesizes the vast majority of the body's serotonin. As a specialized mechanosensor, the EC cell releases this serotonin in response to mechanical forces. However, the molecular mechanism of EC cell mechanotransduction is unknown. In the present study, we show, for the first time, that the mechanosensitive ion channel Piezo2 is specifically expressed by the human and mouse EC cells. Activation of Piezo2 by mechanical forces results in a characteristic ionic current, the release of serotonin and stimulation of gastrointestinal secretion. Piezo2 inhibition by drugs or molecular knockdown decreases mechanosensitive currents, serotonin release and downstream physiological effects. The results of the present study suggest that the mechanosensitive ion channel Piezo2 is specifically expressed by the EC cells of the human and mouse small bowel and that it is important for EC cell mechanotransduction. ABSTRACT: The enterochromaffin (EC) cell in the gastrointestinal (GI) epithelium is the source of nearly all systemic serotonin (5-hydroxytryptamine; 5-HT), which is an important neurotransmitter and endocrine, autocrine and paracrine hormone. The EC cell is a specialized mechanosensor, and it is well known that it releases 5-HT in response to mechanical forces. However, the EC cell mechanotransduction mechanism is unknown. The present study aimed to determine whether Piezo2 is involved in EC cell mechanosensation. Piezo2 mRNA was expressed in human jejunum and mouse mucosa from all segments of the small bowel. Piezo2 immunoreactivity localized specifically within EC cells of human and mouse small bowel epithelium. The EC cell model released 5-HT in response to stretch, and had Piezo2 mRNA and protein, as well as a mechanically-sensitive inward non-selective cation current characteristic of Piezo2. Both inward currents and 5-HT release were inhibited by Piezo2 small interfering RNA and antagonists (Gd3+ and D-GsMTx4). Jejunum mucosal pressure increased 5-HT release and short-circuit current via submucosal 5-HT3 and 5-HT4 receptors. Pressure-induced secretion was inhibited by the mechanosensitive ion channel antagonists gadolinium, ruthenium red and D-GsMTx4. We conclude that the EC cells in the human and mouse small bowel GI epithelium selectively express the mechanosensitive ion channel Piezo2, and also that activation of Piezo2 by force leads to inward currents, 5-HT release and an increase in mucosal secretion. Therefore, Piezo2 is critical to EC cell mechanosensitivity and downstream physiological effects.

Effectiveness of hands-on tutoring and guided self-directed learning versus self-directed learning alone to educate critical care fellows on mechanical ventilation - a pilot project.

BACKGROUND: Physicians require extensive training to achieve proficiency in mechanical ventilator (MV) management of the critically ill patients. Guided self-directed learning (GSDL) is usually the method used to learn. However, it is unclear if this is the most proficient approach to teaching mechanical ventilation to critical care fellows. We, therefore, investigated whether critical care fellows achieve higher scores on standardized testing and report higher satisfaction after participating in a hands-on tutorial combined with GSDL compared to self-directed learning alone. METHODS: First-year Pulmonary and Critical Care Medicine (PCCM) fellows (n=6) and Critical Care Internal Medicine (CCIM) (n=8) fellows participated. Satisfaction was assessed using the Likert scale. MV knowledge assessment was performed by administering a standardized 25-question multiple choice pre- and posttest. For 2 weeks the CCIM fellows were exposed to GSDL, while the PCCM fellows received hands-on tutoring combined with GSDL. RESULTS: Ninety-three percentage (6 PCCM and 7 CCIM fellows, total of 13 fellows) completed all evaluations and were included in the final analysis. CCIM and PCCM fellows scored similarly in the pretest (64% vs. 52%, p=0.13). Following interventions, the posttest scores increased in both groups. However, no significant difference was observed based on the interventions (74% vs. 77%, p=0.39). The absolute improvement with the hands-on-tutoring and GSDL group was higher than GSDL alone (25% vs. 10%, p=0.07). Improved satisfaction scores were noted with hands-on tutoring. CONCLUSIONS: Hands-on tutoring combined with GSDL and GSDL alone were both associated with an improvement in posttest scores. Absolute improvement in test and satisfaction scores both trended higher in the hands-on tutorial group combined with GSDL group.

Refractory Hypoxemia and Use of Rescue Strategies. A U.S. National Survey of Adult Intensivists.

RATIONALE: The management of severe and refractory hypoxemia in critically ill adult patients is practice based. Variability across individual practitioners and institutions is not well documented. OBJECTIVES: To conduct a nationwide survey of critical care physicians in the United States regarding accepted definitions and management strategies for severe and refractory hypoxemia. METHODS: A web-based survey was distributed to a stratified random sample of adult intensivists listed in the American Medical Association Physician Masterfile. The survey was generated by using a mixed-methods approach. MEASUREMENTS AND MAIN RESULTS: In the survey, 4,865 e-mails were sent and 791 (16.3%) were opened. Among those who opened the e-mail message, 50% (n = 396) responded, representing 8.1% of total surveys sent. Seventy-two percent stated that their institutions lacked a protocol for identification and management of severe or refractory hypoxemia in the setting of acute respiratory failure. While the majority of respondents used low-Vt ventilation (81%), high positive end-expiratory pressure (86%), recruitment maneuvers (89%), and either bolus or infusion neuromuscular blockade (94%), there was marked variability in the use of specific rescue strategies as tier 1 or 2 interventions: prone position (27.8% vs. 47.8%, respectively), extracorporeal membrane oxygenation (2.3% vs. 51.2%, respectively), airway pressure release ventilation (49% vs. 34.5%, respectively), inhaled vasodilators (30.1% vs. 40%, respectively), and high-frequency oscillatory ventilation (7.8% vs. 40%, respectively). The variability was partly explained by providers' expertise with particular rescue strategies (77.7%), advance directives (70.1%), the training of allied health staff (62.3%), and institutional availability (53.8%). CONCLUSIONS: U.S. adult critical care physicians predominantly employ lung-protective ventilation for severe hypoxemia. A wide variation in other rescue strategies is noted, which is partly explained by user expertise and availability. Less than 30% institutions have formal protocols for management of refractory hypoxemia.

TRIM72 modulates caveolar endocytosis in repair of lung cells.

Alveolar epithelial and endothelial cell injury is a major feature of the acute respiratory distress syndrome, in particular when in conjunction with ventilation therapies. Previously we showed [Kim SC, Kellett T, Wang S, Nishi M, Nagre N, Zhou B, Flodby P, Shilo K, Ghadiali SN, Takeshima H, Hubmayr RD, Zhao X. Am J Physiol Lung Cell Mol Physiol 307: L449-L459, 2014.] that tripartite motif protein 72 (TRIM72) is essential for amending alveolar epithelial cell injury. Here, we posit that TRIM72 improves cellular integrity through its interaction with caveolin 1 (Cav1). Our data show that, in primary type I alveolar epithelial cells, lack of TRIM72 led to significant reduction of Cav1 at the plasma membrane, accompanied by marked attenuation of caveolar endocytosis. Meanwhile, lentivirus-mediated overexpression of TRIM72 selectively increases caveolar endocytosis in rat lung epithelial cells, suggesting a functional association between these two. Further coimmunoprecipitation assays show that deletion of either functional domain of TRIM72, i.e., RING, B-box, coiled-coil, or PRY-SPRY, abolishes the physical interaction between TRIM72 and Cav1, suggesting that all theoretical domains of TRIM72 are required to forge a strong interaction between these two molecules. Moreover, in vivo studies showed that injurious ventilation-induced lung cell death was significantly increased in knockout (KO) TRIM72(KO) and Cav1(KO) lungs compared with wild-type controls and was particularly pronounced in double KO mutants. Apoptosis was accompanied by accentuation of gross lung injury manifestations in the TRIM72(KO) and Cav1(KO) mice. Our data show that TRIM72 directly and indirectly modulates caveolar endocytosis, an essential process involved in repair of lung epithelial cells through removal of plasma membrane wounds. Given TRIM72's role in endomembrane trafficking and cell repair, we consider this molecule an attractive therapeutic target for patients with injured lungs.