Dataset Information

The impact of fluid status and decremental PEEP strategy on cardiac function and lung and kidney damage in mild-moderate experimental acute respiratory distress syndrome.

ABSTRACT:

Background

We evaluated the effects of abrupt versus gradual PEEP decrease, combined with standard versus high-volume fluid administration, on cardiac function, as well as lung and kidney damage in an established model of mild-moderate acute respiratory distress syndrome (ARDS).

Methods

Wistar rats received endotoxin intratracheally. After 24 h, they were treated with Ringer's lactate at standard (10 mL/kg/h) or high (30 mL/kg/h) dose. For 30 min, all animals were mechanically ventilated with tidal volume = 6 mL/kg and PEEP = 9 cmH₂O (to keep alveoli open), then randomized to undergo abrupt or gradual (0.2 cmH₂O/min for 30 min) PEEP decrease from 9 to 3 cmH₂O. Animals were then further ventilated for 10 min at PEEP = 3 cmH₂O, euthanized, and their lungs and kidneys removed for molecular biology analysis.

Results

At the end of the experiment, left and right ventricular end-diastolic areas were greater in animals treated with high compared to standard fluid administration, regardless of PEEP decrease rate. However, pulmonary arterial pressure, indicated by the pulmonary acceleration time (PAT)/pulmonary ejection time (PET) ratio, was higher in abrupt compared to gradual PEEP decrease, independent of fluid status. Animals treated with high fluids and abrupt PEEP decrease exhibited greater diffuse alveolar damage and higher expression of interleukin-6 (a pro-inflammatory marker) and vascular endothelial growth factor (a marker of endothelial cell damage) compared to the other groups. The combination of standard fluid administration and gradual PEEP decrease increased zonula occludens-1 expression, suggesting epithelial cell preservation. Expression of club cell-16 protein, an alveolar epithelial cell damage marker, was higher in abrupt compared to gradual PEEP decrease groups, regardless of fluid status. Acute kidney injury score and gene expression of kidney injury molecule-1 were higher in the high versus standard fluid administration groups, regardless of PEEP decrease rate.

Conclusion

In the ARDS model used herein, decreasing PEEP abruptly increased pulmonary arterial hypertension, independent of fluid status. The combination of abrupt PEEP decrease and high fluid administration led to greater lung and kidney damage. This information adds to the growing body of evidence that supports gradual transitioning of ventilatory patterns and warrants directing additional investigative effort into vascular and deflation issues that impact lung protection.

SUBMITTER: Rocha NN

PROVIDER: S-EPMC8323327 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BACKGROUND:A large proportion of patients with a SARS-Cov-2-associated respiratory failure develop an acute respiratory distress syndrome (ARDS). It has been recently suggested that SARS-Cov-2-associated ARDS may differ from usual non-SARS-Cov-2-associated ARDS by higher respiratory system compliance (CRS), lower potential for recruitment with positive end-expiratory pressure (PEEP) contrasting with severe shunt fraction. The purpose of the study was to systematically assess respiratory mechanics and recruitability in SARS-Cov-2-associated ARDS. METHODS:Gas exchanges, CRS and hemodynamics were assessed at 2 levels of PEEP (15 cmH2O and 5 cmH2O) within 36 h (day1) and from 4 to 6 days (day 5) after intubation. The recruited volume was computed as the difference between the volume expired from PEEP 15 to 5 cmH2O and the volume predicted by compliance at PEEP 5 cmH2O (or above airway opening pressure). The recruitment-to-inflation (R/I) ratio (i.e. the ratio between the recruited lung compliance and CRS at PEEP 5 cmH2O) was used to assess lung recruitability. A R/I ratio value higher than or equal to 0.5 was used to define highly recruitable patients. RESULTS:The R/I ratio was calculated in 25 of the 26 enrolled patients at day 1 and in 15 patients at day 5. At day 1, 16 (64%) were considered as highly recruitable (R/I ratio median [interquartile range] 0.7 [0.55-0.94]) and 9 (36%) were considered as poorly recruitable (R/I ratio 0.41 [0.31-0.48]). The PaO2/FiO2 ratio at PEEP 15 cmH2O was higher compared to PEEP 5 cmH2O only in highly recruitable patients (173 [139-236] vs 135 [89-167] mmHg; p < 0.01). Neither PaO2/FiO2 or CRS measured at PEEP 15 cmH2O or at PEEP 5 cmH2O nor changes in PaO2/FiO2 or CRS in response to PEEP changes allowed to identify highly or poorly recruitable patients. CONCLUSION:In this series of 25 patients with SARS-Cov-2 associated ARDS, 64% were considered as highly recruitable and only 36% as poorly recruitable based on the R/I ratio performed on the day of intubation. This observation suggests that a systematic R/I ratio assessment may help to guide initial PEEP titration to limit harmful effect of unnecessary high PEEP in the context of Covid-19 crisis.

Project description:BackgroundFluid overload (FO) is associated with unfavorable outcomes in critically ill children. Clinicians are encouraged to avoid FO; however, strategies to avoid FO are not well-described in pediatrics. Our aim was to implement a bundle strategy to prevent FO in children with sepsis and pARDS and to compare the outcomes with a historical cohort.MethodsA quality improvement initiative, known as preemptive fluid strategy (PFS) was implemented to prevent early FO, in a 12-bed general PICU. Infants on mechanical ventilation (MV) fulfilling pARDS and sepsis criteria were prospectively recruited. For comparison, data from a historical cohort from 2015, with the same inclusion and exclusion criteria, was retrospectively reviewed. The PFS bundle consisted of 1. maintenance of intravenous fluids (MIVF) at 50% of requirements; 2. drug volume reduction; 3. dynamic monitoring of preload markers to determine the need for fluid bolus administration; 4. early use of diuretics; and 5. early initiation of enteral feeds. The historical cohort treatment, the standard fluid strategy (SFS), were based on physician preferences. Peak fluid overload (PFO) was the primary outcome. PFO was defined as the highest FO during the first 72 h. FO was calculated as (cumulative fluid input - cumulative output)/kg*100. Fluid input/output were registered every 12 h for 72 h.ResultsThirty-seven patients were included in the PFS group (54% male, 6 mo (IQR 2,11)) and 39 with SFS (64%male, 3 mo (IQR1,7)). PFO was lower in PFS (6.31% [IQR4.4-10]) compared to SFS (12% [IQR8.4-15.8]). FO was lower in PFS compared to CFS as early as 12 h after admission [2.4(1.4,3.7) v/s 4.3(1.5,5.5), p < 0.01] and maintained during the study. These differences were due to less fluid input (MIVF and fluid boluses). There were no differences in the renal function test. PRBC requirements were lower during the first 24 h in the PFS (5%) compared to SFS (28%, p < 0.05). MV duration was 81 h (58,98) in PFS and 118 h (85154) in SFS(p < 0.05). PICU LOS in PFS was 5 (4, 7) and in SFS was 8 (6, 10) days.ConclusionImplementation of a bundle to prevent FO in children on MV with pARDS and sepsis resulted in less PFO. We observed a decrease in MV duration and PICU LOS. Future studies are needed to address if PFS might have a positive impact on health outcomes.

Project description:ImportanceAdjusting positive end-expiratory pressure (PEEP) to offset pleural pressure might attenuate lung injury and improve patient outcomes in acute respiratory distress syndrome (ARDS).ObjectiveTo determine whether PEEP titration guided by esophageal pressure (PES), an estimate of pleural pressure, was more effective than empirical high PEEP-fraction of inspired oxygen (Fio2) in moderate to severe ARDS.Design, setting, and participantsPhase 2 randomized clinical trial conducted at 14 hospitals in North America. Two hundred mechanically ventilated patients aged 16 years and older with moderate to severe ARDS (Pao2:Fio2 ≤200 mm Hg) were enrolled between October 31, 2012, and September 14, 2017; long-term follow-up was completed July 30, 2018.InterventionsParticipants were randomized to PES-guided PEEP (n = 102) or empirical high PEEP-Fio2 (n = 98). All participants received low tidal volumes.Main outcomes and measuresThe primary outcome was a ranked composite score incorporating death and days free from mechanical ventilation among survivors through day 28. Prespecified secondary outcomes included 28-day mortality, days free from mechanical ventilation among survivors, and need for rescue therapy.ResultsTwo hundred patients were enrolled (mean [SD] age, 56 [16] years; 46% female) and completed 28-day follow-up. The primary composite end point was not significantly different between treatment groups (probability of more favorable outcome with PES-guided PEEP: 49.6% [95% CI, 41.7% to 57.5%]; P = .92). At 28 days, 33 of 102 patients (32.4%) assigned to PES-guided PEEP and 30 of 98 patients (30.6%) assigned to empirical PEEP-Fio2 died (risk difference, 1.7% [95% CI, -11.1% to 14.6%]; P = .88). Days free from mechanical ventilation among survivors was not significantly different (median [interquartile range]: 22 [15-24] vs 21 [16.5-24] days; median difference, 0 [95% CI, -1 to 2] days; P = .85). Patients assigned to PES-guided PEEP were significantly less likely to receive rescue therapy (4/102 [3.9%] vs 12/98 [12.2%]; risk difference, -8.3% [95% CI, -15.8% to -0.8%]; P = .04). None of the 7 other prespecified secondary clinical end points were significantly different. Adverse events included gross barotrauma, which occurred in 6 patients with PES-guided PEEP and 5 patients with empirical PEEP-Fio2.Conclusions and relevanceAmong patients with moderate to severe ARDS, PES-guided PEEP, compared with empirical high PEEP-Fio2, resulted in no significant difference in death and days free from mechanical ventilation. These findings do not support PES-guided PEEP titration in ARDS.Trial registrationClinicalTrials.gov Identifier NCT01681225.

Project description:Importance:The effects of recruitment maneuvers and positive end-expiratory pressure (PEEP) titration on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remain uncertain. Objective:To determine if lung recruitment associated with PEEP titration according to the best respiratory-system compliance decreases 28-day mortality of patients with moderate to severe ARDS compared with a conventional low-PEEP strategy. Design, Setting, and Participants:Multicenter, randomized trial conducted at 120 intensive care units (ICUs) from 9 countries from November 17, 2011, through April 25, 2017, enrolling adults with moderate to severe ARDS. Interventions:An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory-system compliance (n?=?501; experimental group) or a control strategy of low PEEP (n?=?509). All patients received volume-assist control mode until weaning. Main Outcomes and Measures:The primary outcome was all-cause mortality until 28 days. Secondary outcomes were length of ICU and hospital stay; ventilator-free days through day 28; pneumothorax requiring drainage within 7 days; barotrauma within 7 days; and ICU, in-hospital, and 6-month mortality. Results:A total of 1010 patients (37.5% female; mean [SD] age, 50.9 [17.4] years) were enrolled and followed up. At 28 days, 277 of 501 patients (55.3%) in the experimental group and 251 of 509 patients (49.3%) in the control group had died (hazard ratio [HR], 1.20; 95% CI, 1.01 to 1.42; P?=?.041). Compared with the control group, the experimental group strategy increased 6-month mortality (65.3% vs 59.9%; HR, 1.18; 95% CI, 1.01 to 1.38; P?=?.04), decreased the number of mean ventilator-free days (5.3 vs 6.4; difference, -1.1; 95% CI, -2.1 to -0.1; P?=?.03), increased the risk of pneumothorax requiring drainage (3.2% vs 1.2%; difference, 2.0%; 95% CI, 0.0% to 4.0%; P?=?.03), and the risk of barotrauma (5.6% vs 1.6%; difference, 4.0%; 95% CI, 1.5% to 6.5%; P?=?.001). There were no significant differences in the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality. Conclusions and Relevance:In patients with moderate to severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality. These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients. Trial Registration:clinicaltrials.gov Identifier: NCT01374022.

Project description:Background: Variable pressure support ventilation (vPSV) is an assisted ventilation mode that varies the level of pressure support on a breath-by-breath basis to restore the physiological variability of breathing activity. We aimed to compare the effects of vPSV at different levels of variability and pressure support (ΔP S) in patients with acute respiratory distress syndrome (ARDS). Methods: This study was a crossover randomized clinical trial. We included patients with mild to moderate ARDS already ventilated in conventional pressure support ventilation (PSV). The study consisted of two blocks of interventions, and variability during vPSV was set as the coefficient of variation of the ΔP S level. In the first block, the effects of three levels of variability were tested at constant ΔP S: 0% (PSV0%, conventional PSV), 15% (vPSV15%), and 30% (vPSV30%). In the second block, two levels of variability (0% and variability set to achieve ±5 cmH2O variability) were tested at two ΔPS levels (baseline ΔP S and ΔP S reduced by 5 cmH2O from baseline). The following four ventilation strategies were tested in the second block: PSV with baseline ΔP S and 0% variability (PSVBL) or ±5 cmH2O variability (vPSVBL), PSV with ΔPS reduced by 5 cmH2O and 0% variability (PSV-5) or ±5 cmH2O variability (vPSV-5). Outcomes included gas exchange, respiratory mechanics, and patient-ventilator asynchronies. Results: The study enrolled 20 patients. In the first block of interventions, oxygenation and respiratory mechanics parameters did not differ between vPSV15% and vPSV30% compared with PSV0%. The variability of tidal volume (V T) was higher with vPSV15% and vPSV30% compared with PSV0%. The incidence of asynchronies and the variability of transpulmonary pressure (P L) were higher with vPSV30% compared with PSV0%. In the second block of interventions, different levels of pressure support with and without variability did not change oxygenation. The variability of V T and P L was higher with vPSV-5 compared with PSV-5, but not with vPSVBL compared with PSVBL. Conclusion: In patients with mild-moderate ARDS, the addition of variability did not improve oxygenation at different pressure support levels. Moreover, high variability levels were associated with worse patient-ventilator synchrony. Clinical Trial Registration: www.clinicaltrials.gov, identifier: NCT01683669.