Halogenated Agent Delivery in Porcine Model of Acute Respiratory Distress Syndrome via an Intensive Care Unit Type Device

Summary

We describe a model of hydrochloric acid-induced acute respiratory distress syndrome (ARDS) in piglets receiving sedation with halogenated agents, isoflurane and sevoflurane, through a device used for inhaled intensive care sedation. This model can be used to investigate the biological mechanisms of halogenated agents on lung injury and repair.

Abstract

Acute respiratory distress syndrome (ARDS) is a common cause of hypoxemic respiratory failure and death in critically ill patients, and there is an urgent need to find effective therapies. Preclinical studies have shown that inhaled halogenated agents may have beneficial effects in animal models of ARDS. The development of new devices to administer halogenated agents using modern intensive care unit (ICU) ventilators has significantly simplified the dispensing of halogenated agents to ICU patients. Because previous experimental and clinical research suggested potential benefits of halogenated volatiles, such as sevoflurane or isoflurane, for lung alveolar epithelial injury and inflammation, two pathophysiologic landmarks of diffuse alveolar damage during ARDS, we designed an animal model to understand the mechanisms of the effects of halogenated agents on lung injury and repair. After general anesthesia, tracheal intubation, and the initiation of mechanical ventilation, ARDS was induced in piglets via the intratracheal instillation of hydrochloric acid. Then, the piglets were sedated with inhaled sevoflurane or isoflurane using an ICU-type device, and the animals were ventilated with lung-protective mechanical ventilation during a 4 h period. During the study period, blood and alveolar samples were collected to evaluate arterial oxygenation, the permeability of the alveolar-capillary membrane, alveolar fluid clearance, and lung inflammation. Mechanical ventilation parameters were also collected throughout the experiment. Although this model induced a marked decrease in arterial oxygenation with altered alveolar-capillary permeability, it is reproducible and is characterized by a rapid onset, good stability over time, and no fatal complications.

We have developed a piglet model of acid aspiration that reproduces most of the physiological, biological, and pathological features of clinical ARDS, and it will be helpful to further our understanding of the potential lung-protective effects of halogenated agents delivered through devices used for inhaled ICU sedation.

Introduction

Acute respiratory distress syndrome (ARDS) is a common cause of hypoxemic respiratory failure and death in critically ill patients¹. It is characterized by both diffuse alveolar epithelial and endothelial injuries, leading to increased permeability and pulmonary edema, altered alveolar fluid clearance (AFC), and worsened respiratory distress². The resorption of alveolar edema and recovery from ARDS require epithelial fluid transport through the alveoli to remain intact, which suggests that a therapy improving AFC could be useful^3,4. Although lung-protective venti....

Protocol

The study protocol was approved by the Animal Ethics Committee of the French Ministère de l’Education Nationale, de l’Enseignement Supérieur et de la Recherche (approval number 01505.03) before being registered at preclinicaltrials.eu (Pre-clinical registry identifier PCTE0000129). All procedures were performed in the Centre International de Chirurgie Endoscopique, Université Clermont Auvergne, Clermont-Ferrand, France, in accordance with the Animal Research: Reporting In Vivo Experiments (ARRIVE) guidelines³⁶.

1. Animal preparation and anesthesia

1. Pigl....

Results

For this experiment, 25 piglets were anesthetized and divided in two groups: 12 piglets in the untreated group (SHAM group) and 13 piglets in the acid-injured group (HCl group). No piglet died before the end of the experiment. A two-way repeated-measures analysis of variance (RM-ANOVA) indicated a significant time by group interaction (P < 10⁻⁴) with a detrimental effect of HCl-induced ARDS on PaO₂/FiO₂, compared to sham animals without ARDS (Figure 3

Discussion

This article describes a reproducible experimental model of ARDS induced by the intratracheal instillation of HCl in piglets to investigate the lung-protective effects of halogenated volatiles, such as sevoflurane or isoflurane, delivered using an anesthetic conserving device.

The primary goal of this study was to develop an experimental model of ARDS in which volatile agents could be delivered by an anesthetic conserving device, such as those used in ICU patients. Although some effects of hal.......

Materials

Name	Company	Catalog Number	Comments
Tracheal intubation
Endotracheal tube 6-mm	Covidien	18860
Animal preparation
Central venous catheter 3-lumens catheter (7 French - 16 cm)	Arrow	CV-12703
Pulse contour cardiac output monitor PiCCO catheter (3-5 French - 20 cm)	Getinge Pulsion Medical System	catheter
Warm blankets WarmTouch5300	MedTronic	5300
Monitoring
External monitor IntelliVue MP40	Phillips	MNT 142
Point-of-care blood gas analyzer Epoc® Blood Analysis System	Siemens	20093
Pulse contour cardiac output monitor PiCCO Device PulsioFlex Monitor	Getinge Pulsion Medical System	PulsioFlex
Mechanical ventilation
Ventilator Engström Carestation	General Electrics	Engström
Halogenated anesthetics
Anaconda Syringe	SedanaMedical	26022
Anesthetic conserving device AnaConDa-S	SedanaMedical	26050
Charcoal filter FlurAbsorb	SedanaMedical	26096
Filling Adaptaters	SedanaMedical	26042
Ionomer membrane dryer line Nafion	SedanaMedical	26053
Products
Propofol	Mylan	66617123
Isoflurane	Virbac	QN01AB06
Pentobarbital	PanPharma	68942457
Sevoflurane	Abbvie	N01AB08
Sufentanil	Mylan	62404996