Exogenous Surfactant Therapy for Pediatric Patients with Acute Respiratory Distress Syndrome

Exogenous surfactant administration is currently being tested in patients with the acute respiratory distress syndrome (ARDS). The results of the studies have varied because several factors may influence the host’s response to this therapy. This clinical pilot study was designed to evaluate the safety and efficacy of exogenous surfactant administration in pediatric patients with ARDS. Surfactant was administered to 13 patients with severe lung dysfunction, and eight of these patients experienced a significant improvement in oxygenation after the first dose of surfactant. In these patients the exogenous surfactant was administered within 48 h of the diagnosis of ARDS, whereas in the five patients who did not respond, surfactant was administered several days after the onset of ARDS. Responders also spent fewer days on a mechanical ventilator and less time in intensive care compared with nonresponders. Based on the results of this pilot study, a more appropriate multicentre clinical trial should be designed to evaluate this treatment strategy.

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Effect of low-dose exogenous surfactant on infants with acute respiratory distress syndrome after cardiac surgery: A retrospective analysis

10.21203/rs.2.20740/v4 ◽

2020 ◽

Author(s):

Rongyuan Zhang ◽

Xu Wang ◽

Shoujun Li ◽

Jun Yan

Keyword(s):

Cardiac Surgery ◽

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Low Dose ◽

Distress Syndrome ◽

Exogenous Surfactant ◽

Control Group ◽

Surfactant Treatment ◽

Surfactant Administration

Abstract Background: Acute respiratory distress syndrome (ARDS) in infants undergoing cardiac surgery is associated with significant mortality and prolonged ventilation; surfactant administration may be a useful therapy. The purpose of this study was to evaluate the effect of low-dose exogenous surfactant therapy on infants suffering ARDS after cardiac surgery. Methods: We conducted a case-control study of infants diagnosed with moderate-to-severe ARDS (PaO 2 /FiO 2 < 150) after cardiac surgery. A case was defined as a patient that received surfactant and standard therapy, while a control was defined as a patient that underwent standard therapy. The primary endpoint was the improvement in oxygenation index (OI) after 24-hour of surfactant treatment; and secondary endpoints were the ventilator time and PICU time. Results: Twenty-two infants treated with surfactant were matched with 22 controls. Early low-dose (20mg/kg) surfactant treatment was associated with improved outcomes. After surfactant administration for 24-hour, the surfactant group was much better compared with the control group at the 24-hour in OI (difference in average change from baseline, -6.7 [95% CI, -9.3 to -4.1]) ( P < 0.01) and ventilation index (VI, mean difference, -11.9 [95% CI, -18.1 to -5.7]) ( P < 0.01). Ventilation time and PICU time were significantly shorter in the surfactant group compared with the control group (133.6h±27.2 vs 218.4h±28.7, P < 0.01 ; 10.7d±5.1 vs 17.5d±6.8, P < 0.01). Infants in the surfactant group under 3 months benefit more from OI and VI than the infants over 3 months in a preliminary exploratory analysis. Conclusions: In infants with moderate-to-severe ARDS after cardiac surgery, early low-dose exogenous surfactant treatment could prominently improve oxygenation and reduce mechanical ventilation time and PICU time. Infants younger than 3 months may get more benefit of oxygenation than the older ones. Randomized controlled trials are needed to explore the effect of surfactant to ARDS of cardiac surgical infants.

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Effect of low-dose exogenous surfactant on infants with acute respiratory distress syndrome after cardiac surgery: A retrospective analysis

10.21203/rs.2.20740/v3 ◽

2020 ◽

Author(s):

Rongyuan Zhang ◽

Xu Wang ◽

Shoujun Li ◽

Jun Yan

Keyword(s):

Cardiac Surgery ◽

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Low Dose ◽

Distress Syndrome ◽

Exogenous Surfactant ◽

Control Group ◽

Surfactant Treatment ◽

Surfactant Administration

Abstract Background: Acute respiratory distress syndrome (ARDS) in infants undergoing cardiac surgery is associated with significant mortality and prolonged ventilation; surfactant administration may be a useful therapy. The purpose of this study was to evaluate the effect of low-dose exogenous surfactant therapy on infants suffering ARDS after cardiac surgery. Methods: We conducted a case-control study of infants diagnosed with moderate-to-severe ARDS (PaO2/FiO2 < 150) after cardiac surgery. A case was defined as a patient that received surfactant and standard therapy, while a control was defined as a patient that underwent standard therapy. The primary endpoint was the improvement in oxygenation index (OI) after 24-hour of surfactant treatment; and secondary endpoints were the ventilator time and PICU time. Results: Twenty-two infants treated with surfactant were matched with 22 controls. Early low-dose (20mg/kg) surfactant treatment was associated with improved outcomes. After surfactant administration for 24-hour, the surfactant group was much better compared with the control group at the 24-hour in OI (difference in average change from baseline, -6.7 [95% CI, -9.3 to -4.1]) (P < 0.01) and ventilation index (VI, mean difference, -11.9 [95% CI, -18.1 to -5.7]) (P < 0.01). Ventilation time and PICU time were significantly shorter in the surfactant group compared with the control group (133.6h±27.2 vs 218.4h±28.7, P < 0.01 ; 10.7d±5.1 vs 17.5d±6.8, P < 0.01). Infants in the surfactant group under 3 months benefit more from OI and VI than the infants over 3 months in a preliminary exploratory analysis. Conclusions: In infants with moderate-to-severe ARDS after cardiac surgery, early low-dose exogenous surfactant treatment could prominently improve oxygenation and reduce mechanical ventilation time and PICU time. Infants younger than 3 months may get more benefit of oxygenation than the older ones. Randomized controlled trials are needed to explore the effect of surfactant to ARDS of cardiac surgical infants.

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Ultraprotective ventilation allowed by extracorporeal CO2 removal improves the right ventricular function in acute respiratory distress syndrome patients: a quasi-experimental pilot study

Annals of Intensive Care ◽

10.1186/s13613-020-00784-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Suzanne Goursaud ◽

Xavier Valette ◽

Julien Dupeyrat ◽

Cédric Daubin ◽

Damien du Cheyron

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Pilot Study ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Low Flow ◽

Ventilation Strategy ◽

Quasi Experimental ◽

Rv Function ◽

Ultraprotective Ventilation

Abstract Background Right ventricular (RV) failure is a common complication in moderate-to-severe acute respiratory distress syndrome (ARDS). RV failure is exacerbated by hypercapnic acidosis and overdistension induced by mechanical ventilation. Veno-venous extracorporeal CO2 removal (ECCO2R) might allow ultraprotective ventilation with lower tidal volume (VT) and plateau pressure (Pplat). This study investigated whether ECCO2R therapy could affect RV function. Methods This was a quasi-experimental prospective observational pilot study performed in a French medical ICU. Patients with moderate-to-severe ARDS with PaO2/FiO2 ratio between 80 and 150 mmHg were enrolled. An ultraprotective ventilation strategy was used with VT at 4 mL/kg of predicted body weight during the 24 h following the start of a low-flow ECCO2R device. RV function was assessed by transthoracic echocardiography (TTE) during the study protocol. Results The efficacy of ECCO2R facilitated an ultraprotective strategy in all 18 patients included. We observed a significant improvement in RV systolic function parameters. Tricuspid annular plane systolic excursion (TAPSE) increased significantly under ultraprotective ventilation compared to baseline (from 22.8 to 25.4 mm; p < 0.05). Systolic excursion velocity (S’ wave) also increased after the 1-day protocol (from 13.8 m/s to 15.1 m/s; p < 0.05). A significant improvement in the aortic velocity time integral (VTIAo) under ultraprotective ventilation settings was observed (p = 0.05). There were no significant differences in the values of systolic pulmonary arterial pressure (sPAP) and RV preload. Conclusion Low-flow ECCO2R facilitates an ultraprotective ventilation strategy thatwould improve RV function in moderate-to-severe ARDS patients. Improvement in RV contractility appears to be mainly due to a decrease in intrathoracic pressure allowed by ultraprotective ventilation, rather than a reduction of PaCO2.

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Effect of low-dose exogenous surfactant on infants with acute respiratory distress syndrome after cardiac surgery: A retrospective analysis

10.21203/rs.2.20740/v2 ◽

2020 ◽

Author(s):

Rongyuan Zhang ◽

Xu Wang ◽

Shoujun Li ◽

Jun Yan

Keyword(s):

Cardiac Surgery ◽

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Standard Therapy ◽

Low Dose ◽

Distress Syndrome ◽

Exogenous Surfactant ◽

Control Group ◽

Surfactant Treatment

Abstract Background: To evaluate the effect of low-dose exogenous surfactant therapy on infants suffering acute respiratory distress syndrome (ARDS) after cardiac surgery. Methods: We conducted a retrospective case-control study of infants diagnosed with moderate-severe ARDS after cardiac surgery. A case was defined as a patient that received surfactant and standard therapy, while a control was defined as a patient that underwent standard therapy. The primary endpoint was the improvement in oxygenation index (OI) after 24-hour of surfactant treatment; and secondary endpoints were the ventilator time and PICU time. Results: 22 infants treated with surfactant were matched with 22 controls. Early low-dose (20mg/kg) surfactant treatment was associated with improved outcomes. After surfactant administration for 24-hour, the surfactant group was much better compared with the control group at the 24-hour in OI (difference in average change from baseline, -6.7 [95% CI, -9.3 to -4.1]) (P < 0.01) and VI (mean difference, -11.9 [95% CI, -18.1 to -5.7]) (P < 0.01). Ventilation time and PICU time were significantly shorter in the surfactant group compared with the control group (133.6h±27.2 vs 218.4h±28.7, P < 0.01 ; 10.7d±5.1 vs 17.5d±6.8, P < 0.01). Infants in the surfactant group under 3 months benefit more from OI and VI than the infants over 3 months in a preliminary exploratory analysis.Conclusions: In infants with moderate-severe ARDS after cardiac surgery, early low-dose exogenous surfactant treatment could prominently improve oxygenation and reduce mechanical ventilation time and PICU time. Infants younger than 3 months may get more benefit of oxygenation than the older ones.

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Sulforhodamine B and exogenous surfactant effects on alveolar surface tension under acute respiratory distress syndrome conditions

Journal of Applied Physiology ◽

10.1152/japplphysiol.00422.2020 ◽

2020 ◽

Vol 129 (6) ◽

pp. 1505-1513 ◽

Cited By ~ 1

Author(s):

Tam L. Nguyen ◽

Carrie E. Perlman

Keyword(s):

Surface Tension ◽

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Exogenous Surfactant ◽

Sulforhodamine B ◽

Isolated Lungs ◽

Surfactant Effects ◽

Alveolar Surface

In the acute respiratory distress syndrome (ARDS), lowering surface tension, T, should reduce ventilation injury, yet exogenous surfactant has not reduced mortality. We show with direct T determination in isolated lungs that substances suggested to elevate T in ARDS indeed raise T, and exogenous surfactant reduces T. Further, we extend our previous finding that sulforhodamine B (SRB) reduces T below normal in healthy lungs and show that SRB, too, reduces T under ARDS conditions.

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Utility of Driving Pressure and Mechanical Power to Guide Protective Ventilator Settings in Two Cohorts of Adult and Pediatric Patients With Acute Respiratory Distress Syndrome

Critical Care Medicine ◽

10.1097/ccm.0000000000004372 ◽

2020 ◽

Vol Publish Ahead of Print ◽

Author(s):

Sina Saffaran ◽

Anup Das ◽

John G. Laffey ◽

Jonathan G. Hardman ◽

Nadir Yehya ◽

...

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Pediatric Patients ◽

Distress Syndrome ◽

Driving Pressure ◽

Mechanical Power ◽

Ventilator Settings

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Combining High-Frequency Oscillatory Ventilation and Recruitment Maneuvers in Adults With Early Acute Respiratory Distress Syndrome: The Treatment With Oscillation and an Open Lung Strategy (TOOLS) Trial Pilot Study

Yearbook of Pulmonary Disease ◽

10.1016/s8756-3452(08)70231-7 ◽

2006 ◽

Vol 2006 ◽

pp. 285-286

Author(s):

J.A. Barker

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Pilot Study ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

High Frequency ◽

Distress Syndrome ◽

High Frequency Oscillatory Ventilation ◽

Open Lung ◽

Recruitment Maneuvers ◽

High Frequency Oscillatory

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Sevoflurane for Sedation in Acute Respiratory Distress Syndrome. A Randomized Controlled Pilot Study

American Journal of Respiratory and Critical Care Medicine ◽

10.1164/rccm.201604-0686oc ◽

2017 ◽

Vol 195 (6) ◽

pp. 792-800 ◽

Cited By ~ 42

Author(s):

Matthieu Jabaudon ◽

Pierre Boucher ◽

Etienne Imhoff ◽

Russell Chabanne ◽

Jean-Sébastien Faure ◽

...

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Pilot Study ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Randomized Controlled

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Mesenchymal Stem/Stromal Cells Therapy for Sepsis and Acute Respiratory Distress Syndrome

Seminars in Respiratory and Critical Care Medicine ◽

10.1055/s-0040-1713422 ◽

2020 ◽

Cited By ~ 1

Author(s):

Declan Byrnes ◽

Claire H. Masterson ◽

Antonio Artigas ◽

John G. Laffey

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Stromal Cells ◽

Distress Syndrome ◽

Immune Cell ◽

Therapeutic Potential ◽

Phase Iii ◽

High Morbidity ◽

Lung Dysfunction

AbstractSepsis and acute respiratory distress syndrome (ARDS) constitute devastating conditions with high morbidity and mortality. Sepsis results from abnormal host immune response, with evidence for both pro- and anti-inflammatory activation present from the earliest phases. The “proinflammatory” response predominates initially causing host injury, with later-phase sepsis characterized by immune cell hypofunction and opportunistic superinfection. ARDS is characterized by inflammation and disruption of the alveolar-capillary membrane leading to injury and lung dysfunction. Sepsis is the most common cause of ARDS. Approximately 20% of deaths worldwide in 2017 were due to sepsis, while ARDS occurs in over 10% of all intensive care unit patients and results in a mortality of 30 to 45%. Given the fact that sepsis and ARDS share some—but not all—underlying pathophysiologic injury mechanisms, the lack of specific therapies, and their frequent coexistence in the critically ill, it makes sense to consider therapies for both conditions together. In this article, we will focus on the therapeutic potential of mesenchymal stem/stromal cells (MSCs). MSCs are available from several tissues, including bone marrow, umbilical cord, and adipose tissue. Allogeneic administration is feasible, an important advantage for acute conditions like sepsis or ARDS. They possess diverse mechanisms of action of relevance to sepsis and ARDS, including direct and indirect antibacterial actions, potent effects on the innate and adaptive response, and pro-reparative effects. MSCs can be preactivated thereby potentiating their effects, while the use of their extracellular vesicles can avoid whole cell administration. While early-phase clinical trials suggest safety, considerable challenges exist in moving forward to phase III efficacy studies, and to implementation as a therapy should they prove effective.

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