Effects of therapeutic hypercapnia on the expression and function of γδT cells in transplanted lungs in rats.

OBJECTIVE: To investigate the effect of therapeutic hypercapnia on the expression and function of gamma delta T (γδ T) cells during ischemia-reperfusion injury (IRI) after lung transplantation. METHODS: We randomly divided male Wistar rats into three groups (n = 6 in each group), the control group (group N), the IRI group (group I), and the therapeutic hypercapnia group (group H). We then assessed pulmonary edema, neutrophil infiltration, wet-to-dry (W/D) weight ratio, and microscopic histopathology and separately measured the levels of γδT cell surface antigen (TCR) and Interleukin-17 (IL-17) using flow cytometry and enzyme-linked immunosorbent assays (ELISAs). RESULTS: The infiltration of neutrophils and the expression of TCR and IL-17 were significantly increased in the I group compared to the control, and the biopsy edema in group I was more severe. Arterial partial pressure of oxygen (PaO2) was decreased after reperfusion in group I compared with the control group. W/D weight ratio, neutrophil infiltration, and the expression of TCR and IL-17 decreased drastically in the H group compared to the I group. CONCLUSION: Our findings suggest that γδ T lymphocytes were directly involved in lung injury. In addition, therapeutic hypercapnia effectively reduced the expression of γδ T cells and IL-17, and this has the potential to become a treatment strategy for IRI and an intervention to improve lung function.

Supporting patients with hypercapnia.

Hypercapnia is commonly encountered by general and specialist respiratory clinicians. Patients at risk of developing hypercapnic respiratory failure include those with chronic obstructive pulmonary disease (COPD), obesity and neuromuscular disease. Such patients may present to clinicians acutely unwell on the acute medical take or during an inpatient deterioration, or be identified in the stable outpatient setting. In this review, we provide a practical guide to develop clinicians' knowledge, skills and confidence in promptly recognising and managing hypercapnic respiratory failure, and to promote national ventilation quality standards to encourage consistent delivery of high-quality care and optimise outcomes for patients.

Deventilation Syndrome in COPD Patients Receiving Long-Term Home Noninvasive Ventilation: A Systematic Scoping Review.

The treatment of patients with COPD and chronic hypercapnic respiratory failure using noninvasive ventilation (NIV) is well established. A "deventilation syndrome" (DVS) has been described as acute dyspnea after cessation of NIV therapy. A systematic scoping review reporting according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) searching Embase was conducted in September 2021. A final manual search followed in February 2023. Literature synthesis was blinded using Rayyan by three different reviewers. A total of 2,009 studies were screened. Five studies met the eligibility criteria. Four articles presented original data. Three articles examined potential treatment options. Three studies were prospective; none were randomized. A total of 122 patients were included. DVS was defined differently in all studies. Seventy-four patients were identified to suffer from DVS (48 controls). Patients were evaluated by blood gas analysis, transcutaneous TcCO2 measurement, spirometry, whole-body plethysmography, respiratory muscle assessments, diaphragmatic electromyography, ultrasound, 6-min walk test, polysomnography, and questionnaires. Treatment approaches studied were minimization of "patient-ventilator asynchrony" (PVA) and use of pursed- lip breathing ventilation. Pathophysiological mechanisms discussed were PVA, high inspiratory positive airway pressure, hyperinflation, respiratory muscle impairment, and increased respiratory rates. Compared with controls, patients with DVS appeared to suffer from more severe airway obstruction, hyperinflation, and PaCO2 retention; worse exercise test scores; and poorer quality of life. The available evidence does not allow for definite conclusions about pathophysiological mechanisms, ethology, or therapeutic options. Future studies should focus on a consistent definition and possible pathomechanisms.

Effect of Facemask in Congenital Central Hypoventilation Syndrome.

INTRODUCTION: Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder with a mutation in the PHOX2B gene. Patients need ventilatory support by noninvasive ventilation or tracheostomy to treat alveolar hypoventilation. Patients with CCHS have a defect in chemosensitivity signal integration. Recently, due to the COVID-19 pandemic, the entire world has had to get used to wearing medical masks (MM). OBJECTIVES: The aim of the study was to evaluate the effect of an MM on gas exchange and to determine the role of central and peripheral chemoresponsiveness on the partial pressure of transcutaneous carbon dioxide (PtcCO2) in patients with CCHS wearing an MM. METHODS: This study was based on the analysis of recordings obtained without and with an MM during hospitalization and was conducted to assess the impact of MM on PtcCO2 and SpO2 recordings with the SenTec Digital Monitor and their relationships with peripheral CO2 chemosensitivity obtained during tidal breathing measurement and with the hypercapnic hyperoxic ventilatory response. RESULTS: Sixteen patients were included (13 boys) and were 10.2 (7.5; 18.5) years old. The use of an MM had a negative impact on gas exchange in patients with CCHS. The median PtcCO2 increased significantly. Peripheral chemosensitivity correlated with MM-induced PtcCO2 changes (R = -0.72, p = 0.005), but central chemosensitivity (the hypercapnic ventilator response slope) did not (R = -0.22, p = 0.510). CONCLUSION: The use of an MM had a negative impact on gas exchange in patients with CCHS.

High-flow nasal cannula may prolong the length of hospital stay in patients with hypercapnic acute COPD exacerbation.

BACKGROUND: High-flow nasal cannula (HFNC) is increasingly used in patients with acute exacerbation of COPD (AECOPD). We aimed to confirm whether the baseline bicarbonate is an independent predictor of outcomes in patients with hypercapnic AECOPD receiving HFNC. METHODS: This was a secondary analysis of a multicentre randomised trial that enrolled 330 patients with non-acidotic hypercapnic AECOPD supported by HFNC or conventional oxygen treatment (COT). We compared the length of stay (LOS) in hospital and the rate of non-invasive positive pressure ventilation (NPPV) use according to baseline bicarbonate levels using the log-rank test or Cox proportional hazard model. RESULTS: In the high bicarbonate subgroup (n = 165, bicarbonate 35.0[33.3-37.9] mmol/L, partial pressure of arterial carbon dioxide [PaCO2] 56.8[52.0-62.8] mmHg), patients supported by HFNC had a remarkably prolonged LOS in hospital when compared to COT (HR 1.59[1.16-2.17], p = 0.004), whereas patients in the low bicarbonate subgroup (n = 165, bicarbonate 28.8[27.0-30.4] mmol/L, PaCO2 48.0[46.0-50.0] mmHg) had a comparable LOS in hospital regardless of respiratory support modalities. The rate of NPPV use in patients with high baseline bicarbonate level was significantly higher than that in patients with low baseline bicarbonate level (19.4 % vs. 3.0 %, p < 0.0001). Patients with high bicarbonate level in HFNC group had a lower rate of NPPV use compared to COT group (15.4 % vs. 23.0 %, p = 0.217). CONCLUSIONS: Among patients with non-acidotic hypercapnic AECOPD with high baseline bicarbonate level, HFNC is significantly associated with a prolonged LOS in hospital, which may be due to the reduced escalation of NPPV treatment. TRIAL REGISTRATION: clinicaltrials.gov (NCT03003559).

Home high flow nasal cannula for chronic hypercapnic respiratory failure in COPD: A systematic review and meta-analysis.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) with chronic hypercapnia is usually treated with non-invasive ventilation (NIV). High flow nasal cannula (HFNC) may be an appropriate alternative. However, the efficacy of HFNC in COPD patients with chronic hypercapnia is yet to be optimally summarized. METHODS: We conducted a systematic review and meta-analysis using random effects with inverse variance methods. Randomized controlled trials involving adult COPD patients initiated on HFNC for at least one month were included. Outcomes of interest were all-cause mortality, acute exacerbations, hospitalizations, and change in St. George Respiratory Questionnaire (SGRQ). We assessed the risk of bias using ROB 2.0 and assessed the quality of the evidence using GRADE. RESULTS: We included four randomized trials involving 440 patients. HFNC probably reduces acute exacerbations compared to standard care (RR 0.77 [95 % CI 0.66 to 0.89]; moderate certainty), suggesting 69 fewer acute exacerbations per 1000 patients. HFNC may reduce hospital admissions (RR 0.87 [95 % CI 0.69 to 1.09]; low certainty) and may lower the SGRQ score (MD 8.12 units lower [95 % CI 13.30 to 2.95 lower]; low certainty). However, HFNC may have no effect on mortality (RR 1.22 [95 % CI 0.64 to 2.35]; low certainty). CONCLUSION: HFNC probably reduces acute exacerbations and might reduce hospital admissions in COPD patients with chronic hypercapnia. However, its effect on mortality is uncertain. Future larger RCTs with longer follow-up periods are recommended to provide more robust evidence on the efficacy of HFNC in patients with COPD.

Noninvasive Home Mechanical Ventilation for Stable Hypercapnic COPD: A Clinical Respiratory Review from Canadian Perspectives.

Acute short-term noninvasive ventilation (NIV) for hypercapnic respiratory failure in chronic obstructive pulmonary disease (COPD) has well-established benefits; however, the role of long-term home NIV remains controversial. In the past decade, studies utilizing aggressive NIV settings to maximally reduce carbon dioxide levels (PaCO2) have resulted in several positive clinical trials and led to updated guidelines on home NIV for stable hypercapnic COPD patients. This clinical respiratory review discusses the high-intensity NIV approach, summarizes recent key trials and guidelines pertaining to home NIV in COPD, and considers key clinical questions for future research and application in the Canadian context. With recent evidence and Canadian Thoracic Society (CTS) guidelines supporting the use of NIV in carefully selected COPD patients with persistent daytime hypercapnia, we believe it is time to reconsider our approach.

Home ventilation for patients with end-stage chronic obstructive pulmonary disease.

PURPOSE OF THE REVIEW: The number of patients with end-stage chronic obstructive pulmonary disease (COPD) treated with chronic non-invasive ventilation (NIV) has greatly increased. In this review, the authors summarize the evidence for nocturnal NIV and NIV during exercise. The authors discuss the multidisciplinary and advanced care of patients with end-stage COPD treated with NIV. RECENT FINDINGS: Nocturnal NIV improves gas exchange, health-related quality of life and survival in stable hypercapnic COPD patients. Improvements in care delivery have been achieved by relocating care from the hospital to home based; home initiation of chronic NIV is feasible, non-inferior regarding efficacy and cost-effective compared to in-hospital initiation. However, the effect of NIV on symptoms is variable, and applying optimal NIV for end-stage COPD is complex. While exercise-induced dyspnoea is a prominent complaint in end-stage COPD, nocturnal NIV will not change this. However, NIV applied solely during exercise might improve exercise tolerance and dyspnoea. While chronic NIV is often a long-standing treatment, patient expectations should be discussed early and be managed continuously during the treatment. Further, integration of advance care planning requires a multidisciplinary approach. SUMMARY: Although chronic NIV is an effective treatment in end-stage COPD with persistent hypercapnia, there are still important questions that need to be answered to improve care of these severely ill patients.

Effect of Intensity of Home Noninvasive Ventilation in Individuals With Neuromuscular and Chest Wall Disorders: A Systematic Review and Meta-Analysis of Individual Participant Data

Introduction: Home noninvasive ventilation (NIV), targeting a reduction of carbon dioxide with a combination of sufficient inspiratory support and backup-rate improves outcomes in patients with chronic obstructive pulmonary disease. The aim of this systematic review with individual participant data (IPD) meta-analysis was to evaluate the effects of intensity of home NIV on respiratory outcomes in individuals with slowly progressive neuromuscular (NMD) or chest-wall disorders (CWD). Methods: Controlled, non-controlled and cohort studies indexed between January-2000 and December-2020 were sought from Medline, Embase and the Cochrane Central Register. Outcomes were diurnal PaCO2, PaO2, daily NIV usage, and interface type (PROSPERO-CRD 42021245121). NIV intensity was defined according to the Z-score of the product of pressure support (or tidal volume) and backup-rate. Results: 16 eligible studies were identified; we obtained IPD for 7 studies (176 participants: 113-NMD; 63-CWD). The reduction in PaCO2 was greater with higher baseline PaCO2. NIV intensity per se was not associated with improved PaCO2 except in individuals with CWD and the most severe baseline hypercapnia. Similar results were found for PaO2. Daily NIV usage was associated with improvement in gas exchange but not with NIV intensity. No association between NIV intensity and interface type was found. Conclusion: Following home NIV initiation in NMD or CWD patients, no relationship was observed between NIV intensity and PaCO2, except in individuals with the most severe CWD. The amount of daily NIV usage, rather than intensity, is key to improving hypoventilation in this population during the first few months after introduction of therapy. (AU)

Respiratory Center Function and Its Impact in Obesity Hypoventilation Syndrome Treatment

Introduction: Patients with obesity hypoventilation syndrome (OHS) need treatment with positive pressure either with continuous (CPAP) or double pressure (NIV). The apnea–hypopnea index (AHI) is considered a key data for making therapeutic decisions. We hypothesized that HR may be an useful tool to establish different phenotypes and individualize treatment in patients with OHS. Our objective was to analyze the role of the respiratory center response to hypercapnia (HR) in the adequacy of positive airway pressure therapy. Method: We included subjects with OHS treated with CPAP or NIV according to AHI and baseline pCO2. We analyzed therapeutic effectiveness and treatment changes prioritizing CPAP if AHI>30/h. Therapy was considered adequate if it was effective after two years. HR was measured with the p0.1/pEtCO2 ratio and its capability to select therapy was analyzed. The statistical study was performed by means comparison (Student's t) and multivariate analysis (logistic regression). Results: 67 subjects were included of 68(11) years old, 37 (55%) males, initially 45 (67%) treated with NIV and 22 (33%) with CPAP, one case was excluded and in 25 (38%) the treatment was changed. Finally, CPAP was adequate for 29 subjects (44%) and NIV for 37 (56%). The CPAP group showed AHI 57/h (24) and p0.1/pEtCO2 0.37cmH2O/mmHg (0.23), NIV group AHI 43/h (35) and p0.1/pEtCO2 0.24 (0.15) with p=0.049 and 0.006. In multivariate analysis, p0.1/pEtCO2 (p=0.033) and AHI>30 (p=0.001) were predictors of adequate therapy. Conclusion: Measuring the RH of the respiratory center helps to select the most appropriate treatment for patients with OHS. (AU)

Innovative treatment of hypercapnia with soda lime in COVID-19: a case report.

One of the rare consequences of COVID-19 is increasing blood carbon dioxide, which can lead to unconsciousness, dysrhythmia, and cardiac arrest. Therefore, in COVID-19 hypercarbia, non-invasive ventilation (with Bi-level Positive Airway Pressure, BiPAP) is recommended for treatment. If CO2 does not decrease or continues rising, the patient's trachea must be intubated for supportive hyperventilation with a ventilator (Invasive ventilation). The high morbidity and mortality rate of mechanical ventilation is an important problem of invasive ventilation. We launched an innovative treatment of hypercapnia without invasive ventilation to reduce morbidity and mortality. This new approach could open the window for researchers and therapists to reduce COVID death. To investigate the cause of hypercapnia, we measured the carbon dioxide of the airways (mask and tubes of the ventilator) with a capnograph. Increased carbon dioxide inside the mask and tubes of the device was found in a severely hypercapnic COVID patient in the Intensive Care Unit (ICU). She had a 120kg weight and diabetes disease. Her PaCO2 was 138mmHg. In this condition, she had to be under invasive ventilation and accept its complication or lethal risk but we decreased her PaCO2 with the placement of a soda lime canister in the expiratory pathway to absorb CO2 from the mask and ventilation tube. Her PaCO2 dropped from 138 to 80, and the patient woke up from drowsiness completely without invasive ventilation, the next day. This innovative method continued until PaCO2 reached 55 and she was discharged home 14 days later after curing her COVID. Soda lime is used for carbon dioxide absorption in anesthesia machines and we can research its application in hypercarbia state in ICU to postpone invasive ventilation for treatment of hypercapnia.

Respiratory Center Function and Its Impact in Obesity Hypoventilation Syndrome Treatment.

INTRODUCTION: Patients with obesity hypoventilation syndrome (OHS) need treatment with positive pressure either with continuous (CPAP) or double pressure (NIV). The apnea-hypopnea index (AHI) is considered a key data for making therapeutic decisions. We hypothesized that HR may be an useful tool to establish different phenotypes and individualize treatment in patients with OHS. Our objective was to analyze the role of the respiratory center response to hypercapnia (HR) in the adequacy of positive airway pressure therapy. METHOD: We included subjects with OHS treated with CPAP or NIV according to AHI and baseline pCO2. We analyzed therapeutic effectiveness and treatment changes prioritizing CPAP if AHI>30/h. Therapy was considered adequate if it was effective after two years. HR was measured with the p0.1/pEtCO2 ratio and its capability to select therapy was analyzed. The statistical study was performed by means comparison (Student's t) and multivariate analysis (logistic regression). RESULTS: 67 subjects were included of 68(11) years old, 37 (55%) males, initially 45 (67%) treated with NIV and 22 (33%) with CPAP, one case was excluded and in 25 (38%) the treatment was changed. Finally, CPAP was adequate for 29 subjects (44%) and NIV for 37 (56%). The CPAP group showed AHI 57/h (24) and p0.1/pEtCO2 0.37cmH2O/mmHg (0.23), NIV group AHI 43/h (35) and p0.1/pEtCO2 0.24 (0.15) with p=0.049 and 0.006. In multivariate analysis, p0.1/pEtCO2 (p=0.033) and AHI>30 (p=0.001) were predictors of adequate therapy. CONCLUSION: Measuring the RH of the respiratory center helps to select the most appropriate treatment for patients with OHS.

Acute Hypercapnic Respiratory Failure in COPD.

COPD is a progressive inflammatory process affecting both the airways and alveolar structures of the lungs. Exacerbations of COPD are episodes of acute worsening of this inflammatory process, often triggered by infections. The most severe exacerbations are characterized by substantial air trapping and inspiratory muscle overload, which leads to hypercapnic respiratory failure. Pharmacologic therapies focus on intense bronchodilator administration (usually by aerosol), corticosteroids, and antibiotics. Respiratory life support technologies are often needed for severe exacerbations and range from carefully titrated supplemental O2 administration to positive-pressure ventilation (both invasive and noninvasive). Future life support strategies will likely involve extracorporeal life support technologies.

Home Noninvasive Ventilation for COPD.

Patients with hypercapnic COPD appear to represent a phenotype driven by specific physiology including air trapping and mechanical disadvantage, sleep hypoventilation, and sleep apnea. Such individuals appear to be at high risk for adverse health outcomes. Home noninvasive ventilation (NIV) has been shown to have the potential to help compensate for physiological issues underlying hypercapnia. In contrast to older literature, contemporary clinical trials of home NIV have been shown to improve patient-oriented outcomes including quality of life, hospitalizations, and mortality. Advancements in the use of NIV, including the use of higher inspiratory pressures, may account for recent success. Successful practical application of home NIV thus requires an adequate understanding of patient selection, devices and modes, and strategies for titration. The emergence of telemonitoring holds promise for further improvements in patient care by facilitating titration, promoting adherence, troubleshooting issues, and possibly predicting exacerbations. Given the complexity of home NIV, clinicians and health systems might consider establishment of dedicated home ventilation programs to provide such care. In addition, incorporation of respiratory therapist expertise is likely to improve success. Traditional fee-for-service structures have been a challenge for financing such programs, but ongoing changes toward value-based care are likely to make home NIV programs more feasible.

Lowering PCO2 With Noninvasive Ventilation Is Associated With Improved Survival in Chronic Hypercapnic Respiratory Failure.

BACKGROUND: Chronic hypercapnic respiratory failure is associated with high mortality. Although previous work has demonstrated a mortality improvement with high-intensity noninvasive ventilation in COPD, it is unclear whether a PCO2 reduction strategy is associated with improved outcomes in other populations of chronic hypercapnia. METHODS: The objective of this study was to investigate the association between PCO2 reduction (by using transcutaneous PCO2 as an estimate for PaCO2 and survival in a broad population of individuals treated with noninvasive ventilation for chronic hypercapnia. We hypothesized that reductions in PCO2 would be associated with improved survival. Therefore, we performed a cohort study of all the subjects evaluated from February 2012 to January 2021 for noninvasive ventilation initiation and/or optimization due to chronic hypercapnia at a home ventilation clinic in an academic center. We used multivariable Cox proportional hazard models with time-varying coefficients and PCO2 as a time-varying covariate to test the association between PCO2 and all-cause mortality and when adjusting for known cofounders. RESULTS: The mean ± SD age of 337 subjects was 57 ± 16 years, 37% women, and 85% white. In a univariate analysis, survival probability increased with reductions in PCO2 to < 50 mm Hg after 90 d, and these remained significant after adjusting for age, sex, race, body mass index, diagnosis, Charlson comorbidity index, and baseline PCO2 . In the multivariable analysis, the subjects who had a PaCO2 < 50 mm Hg had a reduced mortality risk of 94% between 90 and 179 d (hazard ratio [HR] 0.06, 95% CI 0.01-0.50), 69% between 180 and 364 d (HR 0.31, 95% CI 0.12-0.79), and 73% for 365-730 d (HR 0.27, 95% CI 0.13-0.56). CONCLUSIONS: Reduction in PCO2 from baseline for subjects with chronic hypercapnia treated with noninvasive ventilation was associated with improved survival. Management strategies should target the greatest attainable reductions in PCO2 .

Comparison of High-Flow Nasal Cannula with Conventional Oxygen Therapy in Patients with Hypercapnic Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Purpose: This study aimed to evaluate the clinical outcomes of high-flow nasal cannula (HFNC) compared with conventional oxygen therapy (COT) in patients with hypercapnic chronic obstructive pulmonary disease (COPD), including arterial partial pressure of carbon dioxide (PaCO2), arterial partial pressure of oxygen (PaO2), respiratory rate (RR), treatment failure, exacerbation rates, adverse events and comfort evaluation. Patients and Methods: PubMed, EMBASE and the Cochrane Library were retrieved from inception to September 30, 2022. Eligible trials were randomized controlled trials and crossover studies comparing HFNC and COT in hypercapnic COPD patients. Continuous variables were reported as mean and standard derivation and calculated by weighted mean differences (MD), while dichotomous variables were shown as frequency and proportion and calculated by odds ratio (OR), with the 95% confidence intervals (Cl). Statistical analysis was performed using RevMan 5.4 software. Results: Eight studies were included, five with acute hypercapnia and three with chronic hypercapnia. In acute hypercapnic COPD, short-term HFNC reduced PaCO2 (MD -1.55, 95% CI: -2.85 to -0.25, I² = 0%, p <0.05) and treatment failure (OR 0.54, 95% CI: 0.33 to 0.88, I² = 0%, p<0.05), but there were no significant differences in PaO2 (MD -0.36, 95% CI: -2.23 to 1.52, I² = 45%, p=0.71) and RR (MD -1.07, 95% CI: -2.44 to 0.29, I² = 72%, p=0.12). In chronic hypercapnic COPD, HFNC may reduce COPD exacerbation rates, but there was no advantage in improving PaCO2 (MD -1.21, 95% CI: -3.81 to 1.39, I² = 0%, p=0.36) and PaO2 (MD 2.81, 95% CI: -1.39 to 7.02, I² = 0%, p=0.19). Conclusion: Compared with COT, short-term HFNC reduced PaCO2 and the need for escalating respiratory support in acute hypercapnic COPD, whereas long-term HFNC reduced COPD exacerbations rates in chronic hypercapnia. HFNC has great potential for treating hypercapnic COPD.

Combined extracorporeal CO2 removal and renal replacement therapy in a pregnant patient with COVID-19: a case report.

Background. Pregnant women are at high risk of Coronavirus disease 2019 (COVID-19) complications, including acute respiratory distress syndrome. Currently, one of the cornerstones in the treatment of this condition is lung-protective ventilation (LPV) with low tidal volumes. However, the occurrence of hypercapnia may limit this ventilatory strategy. So, different extracorporeal CO2 removal (ECCO2R) procedures have been developed. ECCO2R comprises a variety of techniques, including low-flow and high-flow systems, that may be performed with dedicated devices or combined with continuous renal replacement therapy (CRRT). Case description. Here, we report a unique case of a pregnant patient affected by COVID-19 who required extracorporeal support for multiorgan failure. While on LPV, because of the concomitant hypercapnia and acute kidney injury, the patient was treated with an ECCO2R membrane inserted in series after a hemofilter in a CRRT platform. This combined treatment reducing hypercapnia allowed LPV maintenance at the same time while providing kidney replacement and ensuring maternal and fetal hemodynamic stability. Adverse effects consisted of minor bleeding episodes due to the anticoagulation required to maintain the extracorporeal circuit patency. The patient's pulmonary and kidney function progressively recovered, permitting the withdrawal of any extracorporeal treatment. At the 25th gestational week, the patient underwent spontaneous premature vaginal delivery because of placental abruption. She gave birth to an 800-gram female baby, who three days later died because of multiorgan failure related to extreme prematurity. Conclusions. This case supports using ECCO2R-CRRT combined treatment as a suitable approach in the management of complex conditions, such as pregnancy, even in the case of severe COVID-19.