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Continuous insufflation of high flows of humidified gas in healthy sheep results in localized damage to tracheal epithelium

Transtracheal administration of oxygen to patients with COFD can effectively reduce chronic hypoxemia, dyspnea and length of hospitalization. Usually the flows of insufflated gas are low, 0.5 1/min up to 3 1/min [1, 2]. Insufflation of gas at higher flows (up to 8 1/min) has been demonstrated to reduce the amount of dead space and minute ventilation, while improving arterial PCO2 [3, 4]. We assessed the injury to the trachea and lungs of healthy sheep following 48 h of continuous insufflation with humidified gas at high flows.

Methods

We percutaneously positioned a minitracheotomy cannula (4 mm id Portex-Mini Trach II Seldinger, Kent, UK) through the cricothyroid membrane in eight healthy sheep (mean body weight, 29.6 kg). Through the cannula we inserted a Teflon catheter (8 Fr) with a silicon distal tip provided with 12 1-mm holes for gas diffusion. The catheter tip was placed at the carina. Adequate humidification is needed for flow rates over 4 1/min, as the flow is bypassing the upper airways [5]. We delivered the gas at 100% relative humidity close to body temperature. The femoral artery and the right jugular vein were percutaneously cannulated for continuous monitoring of systemic and central venous pressure and for blood sampling.

Sheep were divided into three groups: two sheep received 5 1/min of room air; three received 10 1/min of room air; and three controls did not receive any gas flow. Following 48 h of gas insufflation, sheep were anesthetized and killed with an injection of sodium pentobarbital and KC1. For histologic examination, samples of the trachea were taken from: (i) immediately distal to the minitracheotomy cannula; (ii) middle of the trachea; (iii) level of the tip of the catheter; (iv) level of the right upper lobe bronchus, and (v) level of the left upper lobe of the lung. Each sample included four tracheal rings, and was fixed in 10% formalin. Tissue blocks were dehydrated and embedded in paraffin. Sections (5 μm thick) were stained with hematoxylin-eosin, Mova, pentachrome and periodic acid-Schiff (PAS) methods. Sections from each of the five areas were evaluated by a pathologist for the following microscopic changes: (i) tracheal epithelial injury; (ii) inflammatory reaction; (iii) edema; (iv) vascular congestion, and (v) hemorrhage. These changes were graded as 0 = absent, 1 = mild, 2 = moderate, and 3 = severe.

Results

Group 10 l/min: in all sheep we found severe epithelial damage at level 3 of the trachea; severe inflammation, edema, hemorrhage and infiltration of neutrophils were observed in the submucosa. In two sheep, mild epithelial damage and mild submucosal edema were also seen at level 4. There was no damage at other levels. Group 5 l/min: in both sheep, mild damage was observed at level 3, particularly in the epithelial layer. Control group: no damage was found in any area of the trachea. The lung appeared normal in all three groups. The gas exchange and the hemodynamic parameters remained within normal range throughout the study.

Conclusion

From these results, we conclude that continuous tracheal insufflation for 48 h of humidified room air at 10 1/min causes epithelial and submucosal damage localized to the area of trachea directly adjacent to the tip of the catheter. In the same area, at a low gas flow of 5 1/min, only mild damage was observed. Preliminary results from a new tip made of microporous material seem to exclude that the damage is flow-dependent, suggesting that better diffusion and partitioning of the flow of gas could prevent most of this injury.

References

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Sparacino, M., Cereda, M., Frank, A. et al. Continuous insufflation of high flows of humidified gas in healthy sheep results in localized damage to tracheal epithelium. Crit Care 1 (Suppl 1), P053 (1997). https://doi.org/10.1186/cc3831

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