Hyaluronic acid plasma levels during high versus low tidal volume ventilation in a porcine sepsis model

Background Shedding of the endothelial glycocalyx can be observed regularly during sepsis. Moreover, sepsis may be associated with acute respiratory distress syndrome (ARDS), which requires lung protective ventilation with the two cornerstones of application of low tidal volume and positive end-expiratory pressure. This study investigated the effect of a lung protective ventilation on the integrity of the endothelial glycocalyx in comparison to a high tidal volume ventilation mode in a porcine model of sepsis-induced ARDS. Methods After approval by the State and Institutional Animal Care Committee, 20 male pigs were anesthetized and received a continuous infusion of lipopolysaccharide to induce septic shock. The animals were randomly assigned to either low tidal volume ventilation, high tidal volume ventilation, or no-LPS-group groups and observed for 6 h. In addition to the gas exchange parameters and hematologic analyses, the serum hyaluronic acid concentrations were determined from central venous blood and from pre- and postpulmonary and pre- and postcerebral circulation. Post-mortem analysis included histopathological evaluation and determination of the pulmonary and cerebral wet-to-dry ratios. Results Both sepsis groups developed ARDS within 6 h of the experiment and showed significantly increased serum levels of hyaluronic acid in comparison to the no-LPS-group. No significant differences in the hyaluronic acid concentrations were detected before and after pulmonary and cerebral circulation. There was also no significant difference in the serum hyaluronic acid concentrations between the two sepsis groups. Post-mortem analysis showed no significant difference between the two sepsis groups. Conclusion In a porcine model of septic shock and ARDS, the serum hyaluronic acid levels were significantly elevated in both sepsis groups in comparison to the no-LPS-group. Intergroup comparison between lung protective ventilated and high tidal ventilated animals revealed no significant differences in the serum hyaluronic acid levels.

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Implementation of lung protective ventilation order to improve adherence to low tidal volume ventilation: A RE-AIM evaluation

Journal of Critical Care ◽

10.1016/j.jcrc.2020.09.013 ◽

2020 ◽

Author(s):

Briana Short ◽

Alexis Serra ◽

Abdul Tariq ◽

Vivek Moitra ◽

Daniel Brodie ◽

...

Keyword(s):

Tidal Volume ◽

Protective Ventilation ◽

Lung Protective Ventilation ◽

Low Tidal Volume ◽

Low Tidal Volume Ventilation ◽

Volume Ventilation

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Lung-protective ventilation increases cerebral metabolism and non-inflammatory brain injury in porcine experimental sepsis

BMC Neuroscience ◽

10.1186/s12868-021-00629-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Axel Nyberg ◽

Erik Gremo ◽

Jonas Blixt ◽

Jesper Sperber ◽

Anders Larsson ◽

...

Keyword(s):

Brain Injury ◽

Tidal Volume ◽

Cerebral Metabolism ◽

Protective Ventilation ◽

Cerebral Oxygen ◽

Low Tidal Volume ◽

Sagittal Sinus ◽

High Tidal Volume Ventilation ◽

Volume Ventilation ◽

Volume Group

Abstract Background Protective ventilation with lower tidal volumes reduces systemic and organ-specific inflammation. In sepsis-induced encephalopathy or acute brain injury the use of protective ventilation has not been widely investigated (experimentally or clinically). We hypothesized that protective ventilation would attenuate cerebral inflammation in a porcine endotoxemic sepsis model. The aim of the study was to study the effect of tidal volume on cerebral inflammatory response, cerebral metabolism and brain injury. Nine animals received protective mechanical ventilation with a tidal volume of 6 mL × kg−1 and nine animals were ventilated with a tidal volume of 10 mL × kg−1. During a 6-h experiment, the pigs received an endotoxin intravenous infusion of 0.25 µg × kg−1 × h−1. Systemic, superior sagittal sinus and jugular vein blood samples were analysed for inflammatory cytokines and S100B. Intracranial pressure, brain tissue oxygenation and brain microdialysis were sampled every hour. Results No differences in systemic or sagittal sinus levels of TNF-α or IL-6 were seen between the groups. The low tidal volume group had increased cerebral blood flow (p < 0.001) and cerebral oxygen delivery (p < 0.001), lower cerebral vascular resistance (p < 0.05), higher cerebral metabolic rate (p < 0.05) along with higher cerebral glucose consumption (p < 0.05) and lactate production (p < 0.05). Moreover, low tidal volume ventilation increased the levels of glutamate (p < 0.01), glycerol (p < 0.05) and showed a trend towards higher lactate to pyruvate ratio (p = 0.08) in cerebral microdialysate as well as higher levels of S-100B (p < 0.05) in jugular venous plasma compared with medium–high tidal volume ventilation. Conclusions Contrary to the hypothesis, protective ventilation did not affect inflammatory cytokines. The low tidal volume group had increased cerebral blood flow, cerebral oxygen delivery and cerebral metabolism together with increased levels of markers of brain injury compared with medium–high tidal volume ventilation.

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Predicting Fluid Responsiveness Using Pulse Pressure Variation after Tidal Volume Challenge in Postoperative Patients Receiving Lung Protective Ventilation: A Clinical Trial

10.21203/rs.2.17736/v1 ◽

2019 ◽

Author(s):

Pimsai Kunakorn ◽

Sunthiti Morakul ◽

Tananchai Petnak ◽

Pongsasit Singhatat ◽

Chawika Pisitsak

Keyword(s):

Stroke Volume ◽

Tidal Volume ◽

Fluid Responsiveness ◽

Protective Ventilation ◽

Pressure Variation ◽

Lung Protective Ventilation ◽

Predict Fluid Responsiveness ◽

Low Tidal Volume ◽

Volume Ventilation ◽

Volume Challenge

Abstract Background: Lung protective ventilation with low tidal volume is beneficial in patients with intermediate to high risk of postoperative pulmonary complications. However, during low tidal volume ventilation, pulse pressure variation (PPV) and stroke volume variation (SVV) do not predict fluid responsiveness. We aimed to determine whether changes in PPV and SVV after transient increases in tidal volume can predict fluid responsiveness in these patients. Methods: We recorded 22 measurements from 15 patients who experienced postoperative acute circulatory failure. We performed a tidal volume challenge by transiently increasing tidal volume (VT) from 6 to 8 mL/kg (VT6–8), 8 to 10 mL/kg (VT8–10), and 6 to 10 mL/kg (VT6–10) of patients' predicted body weight. The change in PPV (∆PPV) at VT6–8 (∆PPV6–8), VT8–10 (∆PPV8–10), VT6–10 (∆PPV6–10) and the change in SVV (∆SVV) at VT6–8 (∆SVV6–8), VT8–10 (∆SVV8–10), and VT6–10 (∆SVV6–10) were recorded. Patients were classified as fluid responders if there was an increase in stroke volume of more than 10% after a fluid bolus. Results: Following the tidal volume challenge, ∆PPV and ∆SVV failed to predict fluid responsiveness, with areas under the receiver operating characteristic curves (with 95% confidence intervals) of 0.49 (0.23–0.74), 0.54 (0.29–0.79), 0.52 (0.28–0.77) for ∆PPV6–8, ∆PPV8–10, and ∆PPV6–10, and 0.55 (0.30–0.80), 0.55 (0.31–0.80), and 0.59 (0.34–0.84) for ∆SVV6–8, ∆SVV8–10, and ∆SVV6–10, respectively. Conclusions: Changes in PPV and SVV after the tidal volume challenge did not predict fluid responsiveness in postoperative patients with low tidal volume ventilation. Trial registration: This trial was registered with Clinicaltrials.in.th, TCTR20190808003.

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Lung-Protective Ventilation Increases Cerebral Metabolism and Non-Inflammatory Brain Injury in Porcine Experimental Sepsis

10.21203/rs.3.rs-69382/v1 ◽

2020 ◽

Author(s):

Axel Nyberg ◽

Erik Gremo ◽

Jonas Blixt ◽

Jesper Sperber ◽

Anders Larsson ◽

...

Keyword(s):

Brain Injury ◽

Tidal Volume ◽

Cerebral Metabolism ◽

Protective Ventilation ◽

Cerebral Oxygen ◽

Low Tidal Volume ◽

Sagittal Sinus ◽

High Tidal Volume Ventilation ◽

Volume Ventilation ◽

Volume Group

Abstract Background: Protective ventilation with lower tidal volumes reduces systemic and organ-specific inflammation. In sepsis-induced encephalopathy or acute brain injury the use of protective ventilation has not been widely investigated (experimentally or clinically). We hypothesized that protective ventilation would attenuate cerebral inflammation in a porcine endotoxemic sepsis model. The aim of the study was to study the effect of tidal volume on cerebral inflammatory response, cerebral metabolism and brain injury. Nine animals received protective mechanical ventilation with a tidal volume of 6 mL x kg-1 and nine animals were ventilated with a tidal volume of 10 mL x kg-1. During a 6-hour experiment, the pigs received an endotoxin intravenous infusion of 0.25 µg x kg-1 x h-1. Systemic, superior sagittal sinus and jugular vein blood samples were analysed for inflammatory cytokines and S100B. Intracranial pressure, brain tissue oxygenation and brain microdialysis were sampled every hour. Results: No differences in systemic or sagittal sinus levels of TNF-α or IL-6 were seen between the groups. The low tidal volume group had increased cerebral blood flow (p<0.001) and cerebral oxygen delivery (p<0.001), lower cerebral vascular resistance (p<0.05), higher cerebral metabolic rate (p<0.05) along with higher cerebral glucose consumption (p<0.05) and lactate production (p<0.05). Moreover, low tidal volume ventilation increased the levels of glutamate (p<0.01), glycerol (p<0.08) and showed a trend towards higher lactate to pyruvate ratio (p=0.08) in cerebral microdialysate as well as higher levels of S-100B (p<0.05) in jugular venous plasma compared with medium-high tidal volume ventilation.Conclusions: Contrary to the hypothesis, protective ventilation did not affect inflammatory cytokines. The low tidal volume group had increased cerebral blood flow, cerebral oxygen delivery and cerebral metabolism together with increased levels of markers of brain injury compared with medium-high tidal volume ventilation.

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The Pulmonary Endothelial Glycocalyx Inhibits Nitric Oxide Production from High Tidal Volume Ventilation.

10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a5565 ◽

2009 ◽

Author(s):

EP Schmidt ◽

LE Servinsky ◽

DB Pearse

Keyword(s):

Nitric Oxide ◽

Tidal Volume ◽

Endothelial Glycocalyx ◽

High Tidal Volume ◽

Nitric Oxide Production ◽

Oxide Production ◽

High Tidal Volume Ventilation ◽

Volume Ventilation

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Low Tidal Volume Ventilation in Patients without Acute Respiratory Distress Syndrome: A Paradigm Shift in Mechanical Ventilation

Critical Care Research and Practice ◽

10.1155/2012/416862 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12 ◽

Cited By ~ 7

Author(s):

Jed Lipes ◽

Azadeh Bojmehrani ◽

Francois Lellouche

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Lung Injury ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Tidal Volume ◽

Distress Syndrome ◽

Protective Ventilation ◽

Low Tidal Volume ◽

Low Tidal Volume Ventilation ◽

Volume Ventilation

Protective ventilation with low tidal volume has been shown to reduce morbidity and mortality in patients suffering from acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Low tidal volume ventilation is associated with particular clinical challenges and is therefore often underutilized as a therapeutic option in clinical practice. Despite some potential difficulties, data have been published examining the application of protective ventilation in patients without lung injury. We will briefly review the physiologic rationale for low tidal volume ventilation and explore the current evidence for protective ventilation in patients without lung injury. In addition, we will explore some of the potential reasons for its underuse and provide strategies to overcome some of the associated clinical challenges.

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High tidal volume ventilation induces NOS2 and impairs cAMP- dependent air space fluid clearance

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00331.2002 ◽

2003 ◽

Vol 284 (5) ◽

pp. L791-L798 ◽

Cited By ~ 43

Author(s):

James A. Frank ◽

Jean-François Pittet ◽

Hyon Lee ◽

Micaela Godzich ◽

Michael A. Matthay

Keyword(s):

Lung Injury ◽

Tidal Volume ◽

Time Course ◽

High Tidal Volume ◽

Low Tidal Volume ◽

Edema Fluid ◽

High Tidal Volume Ventilation ◽

Volume Ventilation ◽

Air Space ◽

Induced Changes

Tidal volume reduction during mechanical ventilation reduces mortality in patients with acute lung injury and the acute respiratory distress syndrome. To determine the mechanisms underlying the protective effect of low tidal volume ventilation, we studied the time course and reversibility of ventilator-induced changes in permeability and distal air space edema fluid clearance in a rat model of ventilator-induced lung injury. Anesthetized rats were ventilated with a high tidal volume (30 ml/kg) or with a high tidal volume followed by ventilation with a low tidal volume of 6 ml/kg. Endothelial and epithelial protein permeability were significantly increased after high tidal volume ventilation but returned to baseline levels when tidal volume was reduced. The basal distal air space fluid clearance (AFC) rate decreased by 43% ( P < 0.05) after 1 h of high tidal volume but returned to the preventilation rate 2 h after tidal volume was reduced. Not all of the effects of high tidal volume ventilation were reversible. The cAMP-dependent AFC rate after 1 h of 30 ml/kg ventilation was significantly reduced and was not restored when tidal volume was reduced. High tidal volume ventilation also increased lung inducible nitric oxide synthase (NOS2) expression and air space total nitrite at 3 h. Inhibition of NOS2 activity preserved cAMP-dependent AFC. Because air space edema fluid inactivates surfactant and reduces ventilated lung volume, the reduction of cAMP-dependent AFC by reactive nitrogen species may be an important mechanism of clinical ventilator-associated lung injury.

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