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Individualized positive end-expiratory pressure guided by end-expiratory lung volume in early acute respiratory distress syndrome: study protocol for the multicenter, randomized IPERPEEP trial.

ABSTRACT:

Background

In 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).

Methods

IPERPEEP 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.

Discussion

The 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 registration

ClinicalTrials.gov NCT04012073 . Registered 9 July 2019.

SUBMITTER: Grieco DL

PROVIDER: S-EPMC8772175 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIndividualized positive end-expiratory pressure (PEEP) by electrical impedance tomography (EIT) has potential interest in the optimization of ventilation distribution in acute respiratory distress syndrome (ARDS). The aim of the study was to determine whether early individualized titration of PEEP with EIT improved outcomes in patients with ARDS.MethodsA total of 117 ARDS patients receiving mechanical ventilation were randomly assigned to EIT group (n = 61, PEEP adjusted based on ventilation distribution) or control group (n = 56, low PEEP/FiO2 table). The primary outcome was 28-day mortality. Secondary and exploratory outcomes were ventilator-free days, length of ICU stay, incidence of pneumothorax and barotrauma, and difference in Sequential Organ Failure Assessment (SOFA) score at day 1 (ΔD1-SOFA) and day 2 (ΔD2-SOFA) compared with baseline.Measurements and main resultsThere was no statistical difference in the value of PEEP between the EIT group and control group, but the combination of PEEP and FiO2 was different between groups. In the control group, a significantly positive correlation was found between the PEEP value and the corresponding FiO2 (r = 0.47, p < 0.00001) since a given matched table was used for PEEP settings. Diverse combinations of PEEP and FiO2 were found in the EIT group (r = 0.05, p = 0.68). There was no significant difference in mortality rate (21% vs. 27%, EIT vs. control, p = 0.63), ICU length of stay (13.0 (7.0, 25.0) vs 10.0 (7.0, 14.8), median (25th-75th percentile); p = 0.17), and ventilator-free days at day 28 (14.0 (2.0, 23.0) vs 19.0 (0.0, 24.0), p = 0.55) between the two groups. The incidence of new barotrauma was zero. Compared with control group, significantly lower ΔD1-SOFA and ΔD2-SOFA were found in the EIT group (p < 0.001) in a post hoc comparison. Moreover, the EIT group exhibited a significant decrease of SOFA at day 2 compared with baseline (paired t-test, difference by - 1 (- 3.5, 0), p = 0.001). However, the control group did show a similar decrease (difference by 1 (- 2, 2), p = 0.131).ConclusionOur study showed a 6% absolute decrease in mortality in the EIT group: a statistically non-significant, but clinically non-negligible result. This result along with the showed improvement in organ function might justify further reserach to validate the beneficial effect of individualized EIT-guided PEEP setting on clinical outcomes of patients with ARDS.Trial registrationClinicalTrials, NCT02361398. Registered 11 February 2015-prospectively registered, https://clinicaltrials.gov/show/NCT02361398 .

Project description:BackgroundThe study objective was to compare titration of positive end-expiratory pressure (PEEP) with electrical impedance tomography (EIT) and with ventilator-embedded pressure-volume loop in severe acute respiratory distress syndrome (ARDS).MethodsWe have designed a prospective study with historical control group. Twenty-four severe ARDS patients (arterial oxygen partial pressure to fractional inspired oxygen ratio, PaO2/FiO2 < 100 mmHg) were included in the EIT group and examined prospectively. Data from another 31 severe ARDS patients were evaluated retrospectively (control group). All patients were receiving medical care under identical general support guidelines and protective mechanical ventilation. The PEEP level selected in the EIT group was the intercept point of cumulated collapse and overdistension percentages curves. In the control group, optimal PEEP was selected 2 cmH2O above the lower inflection point on the static pressure-volume curve.ResultsPatients in the EIT group were younger (P < 0.05), and their mean plateau pressure was 1.5 cmH2O higher (P < 0.01). No differences in other baseline parameters such as APACHE II score, PaO2/FiO2, initial PEEP, driving pressure, tidal volume, and respiratory system compliance were found. Two hours after the first PEEP titration, significantly higher PEEP, compliance, and lower driving pressure were found in the EIT group (P < 0.01). Hospital survival rates were 66.7% (16 of 24 patients) in the EIT group and 48.4% (15 of 31) in the control group. Identical rates were found regarding the weaning success rate: 66.7% in the EIT group and 48.4% in the control group.ConclusionIn severe ARDS patients, it was feasible and safe to guide PEEP titration with EIT at the bedside. As compared with pressure-volume curve, the EIT-guided PEEP titration may be associated with improved oxygenation, compliance, driving pressure, and weaning success rate. The findings encourage further randomized control study with a larger sample size and potentially less bias in the baseline data. Trial Registration NCT03112512.

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:BackgroundWe hypothesized that as CARDS may present different pathophysiological features than classic ARDS, the application of high levels of end-expiratory pressure is questionable. Our first aim was to investigate the effects of 5-15 cmH2O of PEEP on partitioned respiratory mechanics, gas exchange and dead space; secondly, we investigated whether respiratory system compliance and severity of hypoxemia could affect the response to PEEP on partitioned respiratory mechanics, gas exchange and dead space, dividing the population according to the median value of respiratory system compliance and oxygenation. Thirdly, we explored the effects of an additional PEEP selected according to the Empirical PEEP-FiO2 table of the EPVent-2 study on partitioned respiratory mechanics and gas exchange in a subgroup of patients.MethodsSixty-one paralyzed mechanically ventilated patients with a confirmed diagnosis of SARS-CoV-2 were enrolled (age 60 [54-67] years, PaO2/FiO2 113 [79-158] mmHg and PEEP 10 [10-10] cmH2O). Keeping constant tidal volume, respiratory rate and oxygen fraction, two PEEP levels (5 and 15 cmH2O) were selected. In a subgroup of patients an additional PEEP level was applied according to an Empirical PEEP-FiO2 table (empirical PEEP). At each PEEP level gas exchange, partitioned lung mechanics and hemodynamic were collected.ResultsAt 15 cmH2O of PEEP the lung elastance, lung stress and mechanical power were higher compared to 5 cmH2O. The PaO2/FiO2, arterial carbon dioxide and ventilatory ratio increased at 15 cmH2O of PEEP. The arterial-venous oxygen difference and central venous saturation were higher at 15 cmH2O of PEEP. Both the mechanics and gas exchange variables significantly increased although with high heterogeneity. By increasing the PEEP from 5 to 15 cmH2O, the changes in partitioned respiratory mechanics and mechanical power were not related to hypoxemia or respiratory compliance. The empirical PEEP was 18 ± 1 cmH2O. The empirical PEEP significantly increased the PaO2/FiO2 but also driving pressure, lung elastance, lung stress and mechanical power compared to 15 cmH2O of PEEP.ConclusionsIn COVID-19 ARDS during the early phase the effects of raising PEEP are highly variable and cannot easily be predicted by respiratory system characteristics, because of the heterogeneity of the disease.

Project description:Background: Different positive end-expiratory pressure (PEEP) strategies are available for subjects with coronavirus disease 2019 (COVID-19)-induced acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation. We aimed to evaluate three conventional PEEP strategies on their effects on respiratory mechanics, gas exchanges, and hemodynamics. Methods: This is a prospective, physiologic, multicenter study conducted in China. We recruited 20 intubated subjects with ARDS and confirmed COVID-19. We first set PEEP by the ARDSnet low PEEP-fraction of inspired oxygen (FIO2) table. After a recruitment maneuver, PEEP was set at 15, 10, and 5 cm H2O for 10 min, respectively. Among these three PEEP levels, best-compliance PEEP was the one providing the highest respiratory system compliance; best-oxygenation PEEP was the one providing the highest PaO2 (partial pressure of arterial oxygen)/FIO2. Results: At each PEEP level, we assessed respiratory mechanics, arterial blood gas, and hemodynamics. Among three PEEP levels, plateau pressure, driving pressure, mechanical power, and blood pressure improved with lower PEEP. The ARDSnet low PEEP-FIO2 table and the best-oxygenation strategies provided higher PEEP than the best-compliance strategy (11 ± 6 cm H2O vs. 11 ± 3 cm H2O vs. 6 ± 2 cm H2O, p = 0.001), leading to higher plateau pressure, driving pressure, and mechanical power. The three PEEP strategies were not significantly different in gas exchange. The subgroup analysis showed that three PEEP strategies generated different effects in subjects with moderate or severe ARDS (n = 12) but not in subjects with mild ARDS (n = 8). Conclusions: In our cohort with COVID-19-induced ARDS, the ARDSnet low PEEP/FIO2 table and the best-oxygenation strategies led to higher PEEP and potentially higher risk of ventilator-induced lung injury than the best-compliance strategy. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04359251.