The Effects of Dexamethasone and Oxygen in Ventilated Adult Sheep with Early Phase Acute Respiratory Distress Syndrome

Engel, Monique; Nowacki, Relana M. E.; Boden, Pim; Reiss, Lucy Kathleen; Uhlig, Stefan; Reynaert, Niki L.; Gopal, Poornima; Wouters, Emiel F.M.; Willems, Coen H. M. P.; Kloosterboer, Nico; Wolfs, Tim G. A. M.; Zimmermann, Luc J. I.; Vos, Gijs D.; Kramer, Boris W.

doi:10.1007/s00408-014-9670-x

Cited by 9 publications

(15 citation statements)

References 32 publications

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“…Nevertheless, our findings are in conflict with another very similar study, where systemic dexamethasone did not have any effect on clinic parameters and lung injury (Engel et al 2015). The discrepancy may be related to different experimental animals used in these studies and varied lung lavage and treatment protocol.…”

Section: Nt Tbarscontrasting

confidence: 99%

Effect of Different Dosages of Dexamethasone Therapy on Lung Function and Inflammation in an Early Phase of Acute Respiratory Distress Syndrome Model

Mikolka

Kosutova²,

M³

et al. 2019

Physiol Res

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Inflammation associated with acute respiratory distress syndrome (ARDS) can damage the alveolar epithelium and surfactant and worsen the respiratory failure. Glucocorticoids (GC) appear to be a rational therapeutic approach, but the effect is still unclear, especially for early administration and low-dose. In this study we compared two low doses of dexamethasone in early phase of surfactant-depleted model of acute respiratory distress syndrome (ARDS). In the study, lung-lavaged New Zealand rabbits with respiratory failure (PaO2<26.7 kPa in FiO2 1.0) were treated with intravenous dexamethasone (DEX): 0.5 mg/kg (DEX-0.5) and 1.0 mg/kg (DEX-1.0), or were untreated (ARDS). Animals without ARDS served as controls. Respiratory parameters, lung edema, leukocyte shifts, markers of inflammation and oxidative damage in the plasma and lung were evaluated. Both doses of DEX improved the lung function vs. untreated animals. DEX-1.0 had faster onset with significant improvement in gas exchange and ventilation efficiency vs. DEX-0.5. DEX-1.0 showed a trend to reduce lung neutrophils, local oxidative damage, and levels of TNFα, IL-6, IL-8 more effectively than DEX-0.5 vs. ARDS group. Both dosages of dexamethasone significantly improved the lung function and suppressed inflammation in early phase ARDS, while some additional enhancement was observed for higher dose (1 mg/kg) of DEX.

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Section: Nt Tbarscontrasting

confidence: 99%

Effect of Different Dosages of Dexamethasone Therapy on Lung Function and Inflammation in an Early Phase of Acute Respiratory Distress Syndrome Model

Mikolka

Kosutova²,

M³

et al. 2019

Physiol Res

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“…One of the most studied therapy has been systemic corticosteroids. Clinical trials on ARDS patients and subsequent meta analyses (Steinberg et al ; Foster ; Yehya et al ; Meduri et al ; Kimura et al ; Tongyoo et al ; Standiford and Ward ; Yang et al ; Fan et al ) as well as experimental studies in animal models of acute lung injury (ALI) (Chen et al ; Leite‐Junior et al ; Wang et al ; Xu et al ; Yubero et al ; Hegeman et al ; Engel et al ) have indicated that glucocorticoids (e.g., methylprednisolone, dexamethasone, hydrocortisone) elicit variable effects as a function of the dose, the route of administration, the time to treatment initiation and duration, the age of the patient, the cause of ARDS/type of ALI model and/or the measured outcomes. Therefore, the available evidence for glucocorticoids benefits in ARDS is conflicting and the use of these treatments in ARDS patients are still subject to debate (Bein et al ; Bihari et al ; Seam and Suffredini ; Thompson and Ranieri ; Mac and McAuley ; Meduri and Siemieniuk ; Bos et al ).…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone fails to improve bleomycin‐induced acute lung injury in mice

et al. 2019

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Acute respiratory distress syndrome (ARDS) features an exudative phase characterized by alveolar damage, lung edema and exacerbated inflammatory response. Given their anti‐inflammatory properties, the potential therapeutic effect of corticosteroids has been evaluated in ARDS clinical trials and experimental models of ALI. These studies produced contradictory results. Therefore, our aim was to investigate the effects of dexamethasone in an animal model of bleomycin‐induced acute lung injury and then to determine if the lack of response could be related to an impairment in repair ability of alveolar epithelial cells after injury. NMRI mice were challenged with bleomycin and then treated daily with dexamethasone or saline. Bronchoalveolar lavages (BAL) and lungs were collected for assessment of the inflammatory response and wet/dry ratio (lung edema) and for histological analyses. The effect of bleomycin and dexamethasone on wound repair was also evaluated in vitro on primary alveolar epithelial cell (ATII) cultures. Our data first showed that dexamethasone treatment did not reduce the weight loss or mortality rates induced by bleomycin. Although the TNF‐α level in BAL of bleomycin‐treated mice was reduced by dexamethasone, the neutrophil infiltration remained unchanged. Dexamethasone also failed to reduce lung edema and damage scores. Finally, bleomycin elicited a time‐ and dose‐dependent reduction in repair rates of ATII cell cultures. This inhibitory effect was further enhanced by dexamethasone, which also affected the expression of β3‐ and β6‐integrins, key proteins of alveolar repair. Altogether, our data indicate that the inability of dexamethasone to improve the resolution of ALI might be due to his deleterious effect on the alveolar epithelium repair.

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“…Plasma from blood samples were collected every 30 min, spun down and stored at -80ºC. After four hours, the animals were euthanized by an intravenous injection of thiopental (18,19). Thoracotomy was performed and the lungs were removed.…”

Section: Experimental Protocolmentioning

confidence: 99%

“…As markers of gas exchange, OI and VEI were calculated from the cardio-respiratory parameters and blood gas analyses before and after lavage, and every 30 minutes during the 4-hour study period (18,19 (20). This was used as marker for in ammation.…”

Section: Experimental Protocolmentioning

confidence: 99%

A comparison of four different models of acute respiratory distress syndrome in sheep

Engel

Nowacki

Jonker

et al. 2020

Preprint

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Background: Acute respiratory distress syndrome (ARDS) can have various causes. The study objective was to investigate whether different pathophysiologic models of ARDS would show different respiratory, cardiovascular and inflammatory outcomes. Methods: We performed a prospective, randomized study in 27 ventilated ewes inducing ARDS using three different techniques to mimic the pulmonary causes of ARDS (ARDSp): warm saline lavage (n=6), intratracheal hydrochloric acid (HCl; n=6), intratracheal albumin (n=10), and one technique to mimic an extrapulmonary cause of ARDS (ARDSexp): intravenous lipopolysaccharide (LPS iv; n=5). ARDS was defined when PaO 2 was <15kPa (112 mmHg) when ventilated with PEEP 10cm H 2 O and FiO 2 =1.0. The effects on gas exchange were investigated by calculating the oxygenation index (OI) and the ventilation efficacy index (VEI) every 30 minutes for a period of 4 hours. Post mortem lung lavage was performed to obtain broncho-alveolar lavage fluid (BALF) to assess lung injury and inflammation. Lung injury and inflammation were assessed by measuring the total number and differentiation of leukocytes, the concentration of protein and disaturated phospholipids, and interleukine-6 and -8 in the BALF. Histology of the lung was evaluated by measuring the mean alveolar size, alveolar wall thickness and the lung injury score system by Matute-Bello et al., as markers of lung injury. The concentration of interleukin-6 was determined in plasma, as a marker of systematic inflammation. Results: The OI and VEI were most affected in the LPS iv group and thereafter the HCl group, after meeting the ARDS criteria. Diastolic blood pressure was lowest in the LPS iv group. There were no significant differences found in the total number and differentiation of leukocytes, the concentration of protein and disaturated phospholipids, or interleukin-8 in the BALF, histology of the lung and the lung injury score. IL-6 in BALF and plasma was highest in the LPS iv group, but no significant differences were found between the other groups. It took a significantly longer period of time to meet the ARDS criteria in the LPS iv group. Conclusions: The LPS model caused the most severe pulmonary and cardiovascular insufficiency. Surprisingly, there were limited significant differences in lung injury and inflammatory markers, despite the different pathophysiological models, when the clinical definition of ARDS was applied.

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The Effects of Dexamethasone and Oxygen in Ventilated Adult Sheep with Early Phase Acute Respiratory Distress Syndrome

Abstract: Our study showed that corticosteroids did not influence inflammation in early phase ARDS and that hyperoxia aggravated lung injury which could not be modulated by dexamethasone in early phase ARDS.

Cited by 9 publications

References 32 publications

Effect of Different Dosages of Dexamethasone Therapy on Lung Function and Inflammation in an Early Phase of Acute Respiratory Distress Syndrome Model

Effect of Different Dosages of Dexamethasone Therapy on Lung Function and Inflammation in an Early Phase of Acute Respiratory Distress Syndrome Model

Dexamethasone fails to improve bleomycin‐induced acute lung injury in mice

A comparison of four different models of acute respiratory distress syndrome in sheep

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