The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.
Adoptive Transfer ; Alveolar Epithelial Cells ; pathology ; Animals ; Apoptosis ; Betacoronavirus ; Body Fluids ; metabolism ; CD4-Positive T-Lymphocytes ; immunology ; Clinical Trials as Topic ; Coinfection ; prevention & control ; therapy ; Coronavirus Infections ; complications ; immunology ; Disease Models, Animal ; Endothelial Cells ; pathology ; Extracorporeal Membrane Oxygenation ; Genetic Therapy ; methods ; Genetic Vectors ; administration & dosage ; therapeutic use ; Humans ; Immunity, Innate ; Inflammation Mediators ; metabolism ; Lung ; pathology ; physiopathology ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stem Cells ; physiology ; Multiple Organ Failure ; etiology ; prevention & control ; Pandemics ; Pneumonia, Viral ; complications ; immunology ; Respiratory Distress Syndrome, Adult ; immunology ; pathology ; therapy ; Translational Medical Research

OBJECTIVETo evaluate the clinical value of the pulse indicator continuous cardiac output (PiCCO) system in patients with severe acute pancreatitis (SAP) complicated with acute respiratory distress syndrome (ARDS).

METHODTwo cases of SAP with ARDS were monitored using PiCCO during comprehensive management in the Pediatric Intensive Care Unit (PICU) of Shengjing Hospital, China Medical University. To guide fluid management, the cardiac index (CI) was measured to assess cardiac function, the global end-diastolic volume index (GEDVI) was used to evaluate cardiac preload, and the extravascular lung water index (EVLWI) was used to evaluate the pulmonary edema.

RESULTCase 1 was diagnosed with type L2 acute lymphoblastic leukemia (intermediate risk) and received the sixth maintenance phases of chemotherapy this time. After a 1-week dosage of chemotherapeutic drugs (pegaspargase and mitoxantrone), he suffered SAP combined with ARDS. Except comprehensive treatment (life supporting, antibiotic, etc.) and applying continuous veno-venous hemodiafiltration (CVVHDF) to remove inflammatory mediators. PiCCO monitor was utilized to guide fluid management. During the early stage of PiCCO monitoring, the patient showed no significant manifestations of pulmonary edema in the bedside chest X-ray (bedside ultrasound showed left pleural effusion), and had an oxygenation index 223 mmHg (1 mmHg = 0.133 kPa), GEDVI 450 ml/m², and ELVWI 7 ml/kg. We increased cardiac output to increase tissue perfusion and dehydration speed of CVVHDF was set at 70 ml/h. Two hours later, GEDVI significantly increased to 600 ml/m² and ELVWI significantly increased to 10 ml/kg, the oxygenation index declined to 155 mmHg, the bedside chest X-ray showed a significant decrease of permeability (right lung) and PEEP was adjusted to 5 cmH₂O (1 cmH₂O = 0.098 kPa), indicating circulating overload. ARDS subsequently occurred, upon which the fluid infusion was halted, the dehydration rate of CVVHDF raised (adjusted to 100-200 ml/h). On day 3 in the PICU, EVLWI dropped to 6 ml/kg, GEDVI dropped to 370 ml/m², and the oxygenation index increased to 180 mmHg. On day 8, the patient was successfully weaned from the ventilator. However, on day 9, the patient reverted to mechanical ventilation due to secondary infection. On day 30, the patient was discharged for voluntarily giving up treatment. Late follow-up results showed that the patient was dead one day after giving up treatment. Case 2 was admitted due to SAP induced by overeating one day before admission. On day 2, the patient showed dyspnea and oxygen saturation decreased to 80%. We applied mechanical ventilation, CVVHDF to remove inflammatory mediators and PiCCO to guide fluid management. According to the initial data of PiCCO, EVLWI was 9 ml/kg, GEDVI was 519 ml/m², the oxygenation index was 298 mmHg, the bedside chest X-ray showed decreased permeability and PEEP was adjusted to 5 cmH₂O, suggesting the existence of ARDS. During treatment, the dehydration speed of CVVHDF was set at 50 ml/h to maintain the balance of fluid input and output. Two hours after PiCCO monitoring, the oxygenation index decreased to 140 mmHg, GEDVI 481 ml/m², EVLWI 9 ml/kg, thus the dehydration speed of CVVHDF was increased (up to 100 ml/h). On day 4 in the PICU, EVLWI was 9 ml/kg, GEDVI was 430 ml/m², oxygenation index was 394 mmHg, and the bedside chest X-ray showed that permeability was higher. On day 5, the patient was transferred from PiCCO. On day 30, the patient recovered and was discharged.

CONCLUSIONPiCCO monitoring can provide real-time surveillance of cardiac function, cardiac preload and afterload, and extravascular lung water in pediatric patients with SAP combined with ARDS. These results are clinically significant for the rescue of critically ill patients with ARDS or shock.

Acute Disease ; Cardiac Output ; physiology ; Child ; China ; Critical Illness ; Extravascular Lung Water ; Fluid Therapy ; Heart ; physiology ; Heart Rate ; Humans ; Lung ; physiology ; Monitoring, Physiologic ; methods ; Pancreatitis ; complications ; physiopathology ; therapy ; Pulmonary Edema ; Respiration, Artificial ; Respiratory Distress Syndrome, Adult ; complications ; physiopathology ; Severity of Illness Index ; Treatment Outcome

OBJECTIVETo investigate the effects of lung protective ventilation strategy combined with lung recruitment maneuver on ARDS complicating patients with severe burn.

METHODSClinical data of 15 severely burned patients with ARDS admitted to our burn ICU from September 2011 to September 2013 and conforming to the study criteria were analyzed. Right after the diagnosis of acute lung injury/ARDS, patients received mechanical ventilation with lung protective ventilation strategy. When the oxygenation index (OI) was below or equal to 200 mmHg (1 mmHg = 0. 133 kPa), lung recruitment maneuver was performed combining incremental positive end-expiratory pressure. When OI was above 200 mmHg, lung recruitment maneuver was stopped and ventilation with lung protective ventilation strategy was continued. When OI was above 300 mmHg, mechanical ventilation was stopped. Before combining lung recruitment maneuver, 24 h after combining lung recruitment maneuver, and at the end of combining lung recruitment maneuver, variables of blood gas analysis (pH, PaO2, and PaCO2) were obtained by blood gas analyzer, and the OI values were calculated; hemodynamic parameters including heart rate, mean arterial pressure (MAP), central venous pressure (CVP) of all patients and the cardiac output (CO), extravascular lung water index (EVLWI) of 4 patients who received pulse contour cardiac output (PiCCO) monitoring were monitored. Treatment measures and outcome of patients were recorded. Data were processed with analysis of variance of repeated measurement of a single group and LSD test.

RESULTS(1) Before combining lung recruitment maneuver, 24 h after combining lung recruitment maneuver, and at the end of combining lung recruitment maneuver, the levels of PaO2 and OI of patients were respectively (77 ± 8), (113 ± 5), (142 ± 6) mmHg, and (128 ± 12), (188 ± 8), (237 ± 10) mmHg. As a whole, levels of PaO2 and OI changed significantly at different time points (with F values respectively 860. 96 and 842. 09, P values below 0. 01); levels of pH and PaCO2 showed no obvious changes (with F values respectively 0.35 and 3.13, P values above 0.05). (2) Levels of heart rate, MAP, CVP of all patients and CO of 4 patients who received PiCCO monitoring showed no significant changes at different time points (with F values from 0. 13 to 4. 26, P values above 0.05). Before combining lung recruitment maneuver, 24 h after combining lung recruitment maneuver, and at the end of combining lung recruitment maneuver, the EVLWI values of 4 patients who received PiCCO monitoring were respectively (13.5 ± 1.3), (10.2 ± 1.0), (7.0 ± 0.8) mL/kg ( F =117.00, P <0.01). (3) The patients received mechanical ventilation at 2 to 72 h after burn, lasting for 14-32 (21 ± 13) d. At post injury day 3-14 (7 ± 5) d, lung recruitment maneuver was applied for 2-5 (3.0 ± 2.0) d. All 15 patients recovered without other complications.

CONCLUSIONSLung protective ventilation strategy combining lung recruitment maneuver can significantly improve the oxygenation in patients with severe burn complicated with ARDS and may therefore improve the prognosis.

Acute Lung Injury ; physiopathology ; therapy ; Blood Gas Analysis ; Burns ; complications ; Extravascular Lung Water ; Hemodynamics ; Humans ; Positive-Pressure Respiration ; Respiration, Artificial ; methods ; Respiratory Distress Syndrome, Adult ; complications ; physiopathology ; therapy ; Treatment Outcome

OBJECTIVETo discuss the distribution of the respiratory complications in severely burned patients and the prevention and treatment experience against them.

METHODSMedical records of 922 adult patients with severe or extremely severe burn hospitalized in our burn ICU from January 2005 to December 2012 were screened and retrospectively analyzed, including patients transferred from other hospitals, patients with total burn area above 50% TBSA, the distribution and treatment of respiratory complications, and the mortality. Data were processed with chi-square test.

RESULTSThe constituent ratio of patients transferred to our hospital was 71.1% in 2007 and 40.2% in 2010, while it remained about 50.0% in the other years. The ratios of patients with total burn area larger than 50% TBSA and that of patients with respiratory complications (χ(2) = 2.637, P > 0.05) showed no significant changes each year. Among these 922 burn patients, 523 patients suffered respiratory complications, among which laryngeal edema (50.9%, 266 cases), pulmonary infection (21.6%, 113 cases), and ARDS (11.9%, 62 cases) were the main components, with no significant change each year (with χ(2) values respectively 6.132, 6.319, 0.016, P values above 0.05). Among the patients with respiratory complications, except for 36 were not treated actively, 487 were treated by ventilator among which 228 had undergone tracheostomy, and the constituent ratios in the 8 years were close. Fifteen patients died, with 2 died of laryngeal edema, 3 of ARDS, and 10 of sepsis or MODS as a result of sepsis.

CONCLUSIONSPatients with severe burns were at high risk of respiratory complications, among which laryngeal edema was common, followed by pulmonary infection and ARDS. Prophylactic tracheostomy, mechanical ventilation, wound therapy, and anti-infection were all effective measures of prevention and treatment against these complications.

Adult ; Aged ; Burns ; complications ; therapy ; Humans ; Laryngeal Edema ; etiology ; physiopathology ; therapy ; Lung ; physiopathology ; Respiration, Artificial ; Respiratory Distress Syndrome, Adult ; etiology ; physiopathology ; therapy ; Retrospective Studies ; Sepsis ; etiology ; physiopathology ; therapy ; Treatment Outcome

OBJECTIVETo investigate the efficacy of continuous blood purification(CBP) in the treatment of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in children.

METHODSOne hundred and forty seven cases of ALI/ARDS were hospitalized to our pediatric intensive care unit, and 32 cases were treated with continuous blood purification (CBP) from June, 2006 to May, 2011. The model for CBP was continuous veno-venous hemofiltration dialysis (CVVHDF). CBP treatment persisted for at least 8 hours and replacement + dialysis fluid dose was 35 - 100 ml/(kg·h). The clinical outcome measures included the mortality rate at 28th day, respiratory index (FiO2/PO2), dynamic lung compliance (Cdyn), arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), mechanical ventilation parameters, vasoactive drug dose and lung X-ray changes.

RESULTSIn totally 147 cases of ALI/ARDS, 89 cases (60.5%) were male and 58 (39.5%) were female, mean age was (43.4 ± 36.7) months. Death occurred in 54 cases, the total mortality was 36.7%. The cause of ALI/ARDS was mainly severe pneumonia, severe sepsis, and leukemia or tumor diseases. There were significant differences in severity of illness between the CBP treatment group and non-CBP treatment group on Pediatric risk of score mortality (PRISM) III score (15.3 vs. 12.7, P < 0.05) and pediatric critical illness score (66.8 ± 19.3 vs. 74.6 ± 17.7, P < 0.05). The average duration of CBP treatment was 52 hours (12 hours to 232 hours). PaO2/FiO2 and Cdyn were improved after 2 hours CBP treatment compared with those before CBP treatment (P < 0.05), mechanical ventilation parameters including fraction of inspired oxygen (FiO2), peak inspiratory pressure (PiP) and positive end expiratory pressure (PEEP) were reduced. The use of vasoactive drugs in patients with MODS and shock gradually declined. The average ventilator-free days of the two groups did not show significant difference (P > 0.05). The mortality on CBP treatment group and non-treatment group were 37.5% and 36.5%, respectively, the difference was not significant (P > 0.05).

CONCLUSIONCBP adjuvant treatment for ALI/ ARDS could reduce pulmonary edema, improve PaO2/FiO2 and Cdyn, and improve mechanical ventilation parameters. CBP may be a very promising treatment for ALI/ARDS in children.

Acute Lung Injury ; physiopathology ; therapy ; Adolescent ; Child ; Child, Preschool ; Female ; Hemofiltration ; methods ; Humans ; Infant ; Intensive Care Units, Pediatric ; Lung Compliance ; Male ; Respiratory Distress Syndrome, Adult ; physiopathology ; therapy ; Treatment Outcome

Patients who are diagnosed with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) usually have ventilation-perfusion mismatch, severe decrease in lung capacity, and gas exchange abnormalities. Health care workers have implemented various strategies in an attempt to compensate for these pathological alterations. By rotating patients with ALI/ARDS between the supine and prone position, it is possible to achieve a significant improvement in PaO2/FiO2, decrease shunting and therefore improve oxygenation without use of expensive, invasive and experimental procedures. Prone positioning is a safe and effective way to improve ventilation when conventional strategies fail to initiate a patient response. Because a specific cure for ARDS is not available, the goal is to support the patients with therapies that cause the least amount of injury while the lungs have an opportunity to heal. Based on current data, a trial of prone positioning ventilation should be offered to the patients who have ALI/ARDS in the early course of the disease. Published studies exhibit substantial heterogeneity in clinical results, suggesting that an adequately sized study optimizing the duration of proning ventilation strategy is warranted to enable definitive conclusions to be drawn.
Acute Lung Injury ; physiopathology ; therapy ; Hemodynamics ; Humans ; Practice Guidelines as Topic ; Prone Position ; Respiration, Artificial ; Respiratory Distress Syndrome, Adult ; physiopathology ; therapy ; Time Factors

BACKGROUNDIt is still controversial as to the implementation of higher positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS). This study was conducted to compare the lower and higher PEEP in patients with ARDS ventilated with low tidal volume, to investigate the relationship between the recruited lung volume by higher PEEP and relevant independent variables and to provide a bedside estimate of the percentage of potentially recruitable lung by higher PEEP.

METHODSTwenty-four patients with ARDS were studied. A lung recruiting maneuver was performed, then each patient was ventilated with PEEP of 8 cmH(2)O for 4 hours and subsequently with PEEP of 16 cmH(2)O for 4 hours. At the end of each PEEP level period, gas exchange, hemodynamic data, lung mechanics, stress index "b" of the dynamic pressure-time curve, intrinsic PEEP and recruited volume by PEEP were measured.

RESULTSFourteen patients were recruiters whose alveolar recruited volumes induced by PEEP 16 cmH(2)O were (425 +/- 65) ml and 10 patients were non-recruiters. Compared with the PEEP 8 cmH(2)O period, after the application of the PEEP 16 cmH(2)O, the PaO(2)/FiO(2) ratio and static lung compliance both remained unchanged in non-recruiters, whereas they increased significantly in recruiters. Changes in PaO(2)/FiO(2) and static lung compliance after PEEP increase were independently associated with the alveolar recruitment. Analyzing the relationship between recruiting maneuver (RM)-induced change in end-expiratory lung volume and the alveolar recruitment induced by PEEP, we found a notable correlation.

CONCLUSIONSThe results of this study indicated that the potential for alveolar recruitment might vary among the ARDS population and the higher PEEP levels should be limited to recruiters. Improving in PaO(2)/FiO(2), static lung compliance after PEEP increase and the shape of the pressure-time curve could be helpful for PEEP application.

Acute Disease ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Positive-Pressure Respiration ; methods ; Pulmonary Gas Exchange ; Respiratory Distress Syndrome, Adult ; physiopathology ; therapy

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), which manifests as non-cardiogenic pulmonary edema, respiratory distress and hypoxemia, could be resulted from various processes that directly or indirectly injure the lung. Extensive investigations in experimental models and humans with ALI/ARDS have revealed many molecular mechanisms that offer therapeutic opportunities for cell or gene therapy. Herein the present strategies and future perspectives of the treatment for ALI/ARDS, include the ventilatory, pharmacological, as well as cell therapies.
Acute Disease ; Animals ; Cell Transplantation ; Genetic Therapy ; Humans ; Lung ; physiopathology ; Lung Injury ; Respiration, Artificial ; Respiratory Distress Syndrome, Adult ; etiology ; physiopathology ; therapy

OBJECTIVETo investigate the relationship of lung stress index and positive end-expiratory pressure (PEEP) at post-recruitment in different canine acute respiratory distress syndrome (ARDS) models.

METHODSThe ARDS models were induced by intravenous oleic acid, saline lavage and hydrochloric acid aspiration in anesthetized dogs. During volume control ventilation with constant inspiratory flow, PEEP was set to obtain a b (stress index) value between 0.9 and 1.1 (b = 1) before and post recruitment maneuver (RM). PEEP was changed to obtain b < 1 (0.6 < b < 0.8) and b > 1 (1.1 < b < 1.3). Meanwhile, the recruited volume (RV) was measured and pulmonary mechanics and gas exchange were observed.

RESULTSAt b = 1 after RM, PEEP were (10.8 +/- 2.3), (12.8 +/- 1.8) and (9.2 +/- 1.8) cm H2O in the oleic acid, saline-lavaged and hydrochloric acid aspiration groups, respectively. PEEP in saline-lavaged group was higher than that in hydrochloric acid aspiration group (P < 0.05). The ratio of partial arterial oxygen tension and fraction of inspiratory oxygen (PaO(2)/FiO(2)) at b = 1 without RM was lower than those post-RM in all three groups (P < 0.05). In oleic acid group, PaO(2)/FiO(2) at b = 1 post-RM was (399 +/- 61) mm Hg, which was higher than that at b < 1 [(307 +/- 71) mm Hg], but there was no difference between those at b = 1 and b > 1. At b = 1 after RM, PaO(2)/FiO(2) in the saline-lavaged group was higher than that in acid aspiration group, but no difference between saline-lavaged group and oleic acid group was found. At b = 1 post-RM, RV were higher than that at b = 1 before RM in all three groups (P < 0.01), but there was no significant difference among three groups. At b = 1 post-RM in three groups, pulmonary compliance were higher than those at b > 1, but airway plateau pressure were lower than those at b > 1.

CONCLUSIONSLung stress index could be a good indicator for PEEP titration at post-RM.

Animals ; Disease Models, Animal ; Dogs ; Female ; Hydrochloric Acid ; pharmacology ; Lung ; physiopathology ; Lung Compliance ; Male ; Oleic Acid ; pharmacology ; Positive-Pressure Respiration ; Respiratory Distress Syndrome, Adult ; chemically induced ; physiopathology ; therapy ; Respiratory Function Tests ; Sodium Chloride ; pharmacology

OBJECTIVETo investigate the efficacy of continuous blood purification (CBP) and to explore its mechanism in the treatment of pediatric septic shock.

METHODSNine children weighted 3.1 kg - 14.0 kg with septic shock were treated with continuous veno-venous hemofiltration (CVVH) which is also referred to as CBP with blood access of double-lumen hemodialysis catheter of 6.5 to 8Fr inserted via central vein, hemofilters of Minifilter plus (for children with body weight < 5 kg) or AV400s (for children with body weight > or = 5 kg), child's type extracorporeal circuit vessel and heparin anticoagulation. The replacement solution was delivered pre-dilution after 3 to 4 hours' post-dilution. The blood gas, clinical biochemical items, medium molecule substance (MMS) concentration in blood as well as capillary refill time (CRT), BP, urine output, vasopressors dosage were examined at a set of time points from the beginning to the end of the CVVH.

RESULTSOf the 9 children, 6 had acute renal failure (ARF), 3 had acute respiratory distress syndrome (ARDS), 5 were blood culture positive and all the 9 needed vasopressors to keep BP before CVVH. The blood pH was 7.14 +/- 0.23, base excess (BE) was -11.3 +/- 4.25 mmol/L, MMS was 3532 +/- 519 U/L, PO2/FiO2 was 188 +/- 33, CRT > 5 s, urine output was 0.85 +/- 0.52 ml/(kg.hr) and the adrenalin dosage 1.36 +/- 0.48 microg/(kg.min), and dopamine 16.35 +/- 3.27 microg/(kg.min) before CVVH. The patients' condition was improved much as demonstrated by pH 7.38 +/- 0.16, BE -0.28 +/- 1.37 mmol/L, MMS 2576 +/- 375 U/L, PO2/FiO2 285 +/- 63, CRT < 2 s, and the adrenalin dosage 0.08 +/- 0.04 microg/(kg.min) and dopamine 8.53 +/- 6.72 microg/(kg.min), urine output 2.9 +/- 1.6 ml/(kg.hr) after 24 hour treatment with CVVH. Of the 9 children, 2 died of MODS (1 intussusception complicated with intestine necrosis, 1 severe scald) and 1 was given up because of severe intestinal fistula, the other 6 children recovered at the end.

CONCLUSIONCBP was effective in treatment of pediatric septic shock by improving the oxygenation, correcting metabolic acidosis, stabilizing BP, increasing the tissue perfusion and eliminating the medium molecule substances.

Acid-Base Equilibrium ; Acute Kidney Injury ; etiology ; physiopathology ; therapy ; Blood Pressure ; Capillaries ; physiopathology ; Child, Preschool ; Female ; Hemofiltration ; methods ; Humans ; Infant ; Male ; Regional Blood Flow ; Respiratory Distress Syndrome, Adult ; etiology ; physiopathology ; therapy ; Severity of Illness Index ; Shock, Septic ; complications ; mortality ; physiopathology ; therapy ; Treatment Outcome