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Effect of positive end-expiratory pressure and tidal volume on lung injury induced by alveolar instability.

ABSTRACT: INTRODUCTION: One potential mechanism of ventilator-induced lung injury (VILI) is due to shear stresses associated with alveolar instability (recruitment/derecruitment). It has been postulated that the optimal combination of tidal volume (Vt) and positive end-expiratory pressure (PEEP) stabilizes alveoli, thus diminishing recruitment/derecruitment and reducing VILI. In this study we directly visualized the effect of Vt and PEEP on alveolar mechanics and correlated alveolar stability with lung injury. METHODS: In vivo microscopy was utilized in a surfactant deactivation porcine ARDS model to observe the effects of Vt and PEEP on alveolar mechanics. In phase I (n = 3), nine combinations of Vt and PEEP were evaluated to determine which combination resulted in the most and least alveolar instability. In phase II (n = 6), data from phase I were utilized to separate animals into two groups based on the combination of Vt and PEEP that caused the most alveolar stability (high Vt [15 cc/kg] plus low PEEP [5 cmH2O]) and least alveolar stability (low Vt [6 cc/kg] and plus PEEP [20 cmH2O]). The animals were ventilated for three hours following lung injury, with in vivo alveolar stability measured and VILI assessed by lung function, blood gases, morphometrically, and by changes in inflammatory mediators. RESULTS: High Vt/low PEEP resulted in the most alveolar instability and lung injury, as indicated by lung function and morphometric analysis of lung tissue. Low Vt/high PEEP stabilized alveoli, improved oxygenation, and reduced lung injury. There were no significant differences between groups in plasma or bronchoalveolar lavage cytokines or proteases. CONCLUSION: A ventilatory strategy employing high Vt and low PEEP causes alveolar instability, and to our knowledge this is the first study to confirm this finding by direct visualization. These studies demonstrate that low Vt and high PEEP work synergistically to stabilize alveoli, although increased PEEP is more effective at stabilizing alveoli than reduced Vt. In this animal model of ARDS, alveolar instability results in lung injury (VILI) with minimal changes in plasma and bronchoalveolar lavage cytokines and proteases. This suggests that the mechanism of lung injury in the high Vt/low PEEP group was mechanical, not inflammatory in nature.

SUBMITTER: Halter JM

PROVIDER: S-EPMC2151879 | biostudies-other | 2007

REPOSITORIES: biostudies-other

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Effect of positive end-expiratory pressure and tidal volume on lung injury induced by alveolar instability.

Halter Jeffrey M JM Steinberg Jay M JM Gatto Louis A LA DiRocco Joseph D JD Pavone Lucio A LA Schiller Henry J HJ Albert Scott S Lee Hsi-Ming HM Carney David D Nieman Gary F GF

Critical care (London, England) 20070101 1

<h4>Introduction</h4>One potential mechanism of ventilator-induced lung injury (VILI) is due to shear stresses associated with alveolar instability (recruitment/derecruitment). It has been postulated that the optimal combination of tidal volume (Vt) and positive end-expiratory pressure (PEEP) stabilizes alveoli, thus diminishing recruitment/derecruitment and reducing VILI. In this study we directly visualized the effect of Vt and PEEP on alveolar mechanics and correlated alveolar stability with ...[more]

PMID: 17302983

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Project description:BackgroundIncreasing functional residual capacity (FRC) or tidal volume (VT) reduces airway resistance and attenuates the response to bronchoconstrictor stimuli in animals and humans. What is unknown is which one of the above mechanisms is more effective in modulating airway caliber and whether their combination yields additive or synergistic effects. To address this question, we investigated the effects of increased FRC and increased VT in attenuating the bronchoconstriction induced by inhaled methacholine (MCh) in healthy humans.MethodsNineteen healthy volunteers were challenged with a single-dose of MCh and forced oscillation was used to measure inspiratory resistance at 5 and 19 Hz (R5 and R19), their difference (R5-19), and reactance at 5 Hz (X5) during spontaneous breathing and during imposed breathing patterns with increased FRC, or VT, or both. Importantly, in our experimental design we held the product of VT and breathing frequency (BF), i.e, minute ventilation (VE) fixed so as to better isolate the effects of changes in VT alone.ResultsTripling VT from baseline FRC significantly attenuated the effects of MCh on R5, R19, R5-19 and X5. Doubling VT while halving BF had insignificant effects. Increasing FRC by either one or two VT significantly attenuated the effects of MCh on R5, R19, R5-19 and X5. Increasing both VT and FRC had additive effects on R5, R19, R5-19 and X5, but the effect of increasing FRC was more consistent than increasing VT thus suggesting larger bronchodilation. When compared at iso-volume, there were no differences among breathing patterns with the exception of when VT was three times larger than during spontaneous breathing.ConclusionsThese data show that increasing FRC and VT can attenuate induced bronchoconstriction in healthy humans by additive effects that are mainly related to an increase of mean operational lung volume. We suggest that static stretching as with increasing FRC is more effective than tidal stretching at constant VE, possibly through a combination of effects on airway geometry and airway smooth muscle dynamics.

Project description:BackgroundIn acute respiratory distress syndrome (ARDS), response to positive end-expiratory pressure (PEEP) is variable according to different degrees of lung recruitability. The search for a tool to individualize PEEP based on patients' individual response is warranted. End-expiratory lung volume (EELV) assessment by nitrogen washing-washout aids bedside estimation of PEEP-induced alveolar recruitment and may therefore help titrate PEEP on patient's individual recruitability. We designed a randomized trial to test whether an individualized PEEP setting protocol driven by EELV measurement may improve a composite clinical outcome in patients with moderate-to-severe ARDS (IPERPEEP trial).MethodsIPERPEEP is an open-label, multicenter, randomized trial that will be conducted in 10 intensive care units in Italy and will enroll 132 ARDS patients showing PaO2/FiO2 ratio ≤ 150 mmHg within 24 h from endotracheal intubation while on mechanical ventilation with PEEP 5 cmH2O. To standardize lung volumes at study initiation, all patients will undergo mechanical ventilation with tidal volume of 6 ml/kg of predicted body weight and PEEP set to obtain a plateau pressure within 28 and 30 cmH2O for 30 min (EXPRESS PEEP). Afterwards, a 5-step decremental PEEP trial will be conducted (EXPRESS PEEP to PEEP 5 cmH2O), and EELV will be measured at each step. Recruitment-to-inflation ratio will be calculated for each PEEP range from EELV difference. Patients will be then randomized to receive mechanical ventilation with PEEP set according to the optimal recruitment observed in the PEEP trial (IPERPEEP arm) trial or to achieve a plateau pressure of 28-30 cmH2O (control arm, EXPRESS strategy). In both groups, tidal volume size, use of prone positioning and neuromuscular blocking agents, and weaning from PEEP and from mechanical ventilation will be standardized. The primary endpoint of the study is a composite clinical outcome incorporating in-ICU mortality, 60-day ventilator-free days, and serum interleukin-6 concentration over the course of the initial 72 h of treatment.DiscussionThe IPERPEEP study is a randomized trial powered to elucidate whether an individualized PEEP setting protocol based on bedside assessment of lung recruitability can improve a composite clinical outcome during moderate-to-severe ARDS.Trial registrationClinicalTrials.gov NCT04012073 . Registered 9 July 2019.

Project description:PURPOSE:Recruitment of lung volume is often cited as the reason for using positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS) patients. We performed a systematic review on PEEP-induced recruited lung volume measured from inspiratory volume-pressure (VP) curves in ARDS patients to assess the prevalence of patients with PEEP-induced recruited lung volume and the mortality in recruiters and non-recruiters. METHODS:We conducted a systematic search of PubMed to identify studies including ARDS patients in which the intervention of an increase in PEEP was accompanied by measurement of the recruited volume (Vrec increase versus no increase) using the VP curve in order to assess the relation between Vrec and mortality at ICU discharge. We first analysed the pooled data from the papers identified and then analysed individual patient level data received from the authors via personal contact. The risk of bias of the included papers was assessed using the quality in prognosis studies tool and the certainty of the evidence regarding the relationship of mortality to Vrec by the GRADE approach. Recruiters were defined as patients with a Vrec?>?150 ml. A random effects model was used for the pooled data. Multivariable logistic regression analysis was used for individual patient data. RESULTS:We identified 16 papers with a total of 308 patients for the pooled data meta-analysis and 14 papers with a total of 384 patients for the individual data analysis. The quality of the articles was moderate. In the pooled data, the prevalence of recruiters was 74% and the mortality was not significantly different between recruiters and non-recruiters (relative risk 1.20 [95% confidence intervals 0.88-1.63]). The certainty of the evidence regarding this association was very low and publication bias evident. In the individual data, the prevalence of recruiters was 70%. In the multivariable logistic regression, Vrec was not associated with mortality but Simplified Acute Physiology Score II and driving pressure at PEEP of 5 cmH2O were. CONCLUSION:After a PEEP increment, most patients are recruiters. Vrec was not associated with ICU mortality. The presence of similar findings in the individual patient level analysis and the driving pressure at PEEP of 5 cmH2O was associated with mortality as previously reported validate our findings. Publication bias and the lack of prospective studies suggest more research is required.

Project description:IntroductionLung-protective ventilation aims at using low tidal volumes (VT) at optimum positive end-expiratory pressures (PEEP). Optimum PEEP should recruit atelectatic lung regions and avoid tidal recruitment and end-inspiratory overinflation. We examined the effect of VT and PEEP on ventilation distribution, regional respiratory system compliance (C(RS)), and end-expiratory lung volume (EELV) in an animal model of acute lung injury (ALI) and patients with ARDS by using electrical impedance tomography (EIT) with the aim to assess tidal recruitment and overinflation.MethodsEIT examinations were performed in 10 anaesthetized pigs with normal lungs ventilated at 5 and 10 ml/kg body weight VT and 5 cmH2O PEEP. After ALI induction, 10 ml/kg VT and 10 cmH2O PEEP were applied. Afterwards, PEEP was set according to the pressure-volume curve. Animals were randomized to either low or high VT ventilation changed after 30 minutes in a crossover design. Ventilation distribution, regional C(RS) and changes in EELV were analyzed. The same measures were determined in five ARDS patients examined during low and high VT ventilation (6 and 10 (8) ml/kg) at three PEEP levels.ResultsIn healthy animals, high compared to low VT increased C(RS) and ventilation in dependent lung regions implying tidal recruitment. ALI reduced C(RS) and EELV in all regions without changing ventilation distribution. Pressure-volume curve-derived PEEP of 21±4 cmH2O (mean±SD) resulted in comparable increase in C(RS) in dependent and decrease in non-dependent regions at both VT. This implied that tidal recruitment was avoided but end-inspiratory overinflation was present irrespective of VT. In patients, regional C(RS) differences between low and high VT revealed high degree of tidal recruitment and low overinflation at 3±1 cmH2O PEEP. Tidal recruitment decreased at 10±1 cmH2O and was further reduced at 15±2 cmH(2)O PEEP.ConclusionsTidal recruitment and end-inspiratory overinflation can be assessed by EIT-based analysis of regional C(RS).

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Effect of positive end-expiratory pressure and tidal volume on lung injury induced by alveolar instability.

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Effect of positive end-expiratory pressure and tidal volume on lung injury induced by alveolar instability.

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