Dataset Information

Sigh in Patients With Acute Hypoxemic Respiratory Failure and ARDS: The PROTECTION Pilot Randomized Clinical Trial.

ABSTRACT:

Background

Sigh is a cyclic brief recruitment maneuver: previous physiologic studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity, and increase release of surfactant.

Research question

Is the clinical application of sigh during pressure support ventilation (PSV) feasible?

Study design and methods

We conducted a multicenter noninferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or ARDS undergoing PSV. Patients were randomized to the no-sigh group and treated by PSV alone, or to the sigh group, treated by PSV plus sigh (increase in airway pressure to 30 cm H₂O for 3 s once per minute) until day 28 or death or successful spontaneous breathing trial. The primary end point of the study was feasibility, assessed as noninferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiologic parameters in the first week from randomization, 28-day mortality, and ventilator-free days.

Results

Two-hundred and fifty-eight patients (31% women; median age, 65 [54-75] years) were enrolled. In the sigh group, 23% of patients failed to remain on assisted ventilation vs 30% in the no-sigh group (absolute difference, -7%; 95% CI, -18% to 4%; P = .015 for noninferiority). Adverse events occurred in 12% vs 13% in the sigh vs no-sigh group (P = .852). Oxygenation was improved whereas tidal volume, respiratory rate, and corrected minute ventilation were lower over the first 7 days from randomization in the sigh vs no-sigh group. There was no significant difference in terms of mortality (16% vs 21%; P = .337) and ventilator-free days (22 [7-26] vs 22 [3-25] days; P = .300) for the sigh vs no-sigh group.

Interpretation

Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk.

Trial registry

ClinicalTrials.gov; No.: NCT03201263; URL: www.clinicaltrials.gov.

SUBMITTER: Mauri T

PROVIDER: S-EPMC7664474 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundInhaled nitric oxide (INO), a selective pulmonary vasodilator, has revolutionized the treatment of neonatal hypoxemic respiratory failure (NHRF). However, there is lack of sustained improvement in 30 to 46% of infants. Aerosolized prostaglandins I2 (PGI2) and E1 (PGE1) have been reported to be effective selective pulmonary vasodilators. The objective of this study was to evaluate the feasibility of a randomized controlled trial (RCT) of inhaled PGE1 (IPGE1) in NHRF.MethodsTwo pilot multicenter phase II RCTs are included in this report. In the first pilot, late preterm and term neonates with NHRF, who had an oxygenation index (OI) of ?15 and <25 on two arterial blood gases and had not previously received INO, were randomly assigned to receive two doses of IPGE1 (300 and 150 ng/kg/min) or placebo. The primary outcome was the enrollment of 50 infants in six to nine months at 10 sites. The first pilot was halted after four months for failure to enroll a single infant. The most common cause for non-enrollment was prior initiation of INO. In a re-designed second pilot, co-administration of IPGE1 and INO was permitted. Infants with suboptimal response to INO received either aerosolized saline or IPGE1 at a low (150 ng/kg/min) or high dose (300 ng/kg/min) for a maximum duration of 72 hours. The primary outcome was the recruitment of an adequate number of patients (n?=?50) in a nine-month-period, with fewer than 20% protocol violations.ResultsNo infants were enrolled in the first pilot. Seven patients were enrolled in the second pilot; three in the control, two in the low-dose IPGE1, and two in the high-dose IPGE1 groups. The study was halted for recruitment futility after approximately six months as enrollment targets were not met. No serious adverse events, one minor protocol deviation and one pharmacy protocol violation were reported.ConclusionsThese two pilot RCTs failed to recruit adequate eligible newborns with NHRF. Complex management RCTs of novel therapies for persistent pulmonary hypertension of the newborn (PPHN) may require novel study designs and a longer period of time from study approval to commencement of enrollment.Trial registrationCLINICALTRIALS.GOV: Pilot one: NCT number: 00598429 registered on 10 January 2008. Last updated: 3 February 2011. Pilot two: NCT number: 01467076 17 October 2011. Last updated: 13 February 2013.

Project description:BackgroundInsufficient or excessive respiratory effort during acute hypoxemic respiratory failure (AHRF) increases the risk of lung and diaphragm injury. We sought to establish whether respiratory effort can be optimized to achieve lung- and diaphragm-protective (LDP) targets (esophageal pressure swing - 3 to - 8 cm H2O; dynamic transpulmonary driving pressure ≤ 15 cm H2O) during AHRF.MethodsIn patients with early AHRF, spontaneous breathing was initiated as soon as passive ventilation was not deemed mandatory. Inspiratory pressure, sedation, positive end-expiratory pressure (PEEP), and sweep gas flow (in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO)) were systematically titrated to achieve LDP targets. Additionally, partial neuromuscular blockade (pNMBA) was administered in patients with refractory excessive respiratory effort.ResultsOf 30 patients enrolled, most had severe AHRF; 16 required VV-ECMO. Respiratory effort was absent in all at enrolment. After initiating spontaneous breathing, most exhibited high respiratory effort and only 6/30 met LDP targets. After titrating ventilation, sedation, and sweep gas flow, LDP targets were achieved in 20/30. LDP targets were more likely to be achieved in patients on VV-ECMO (median OR 10, 95% CrI 2, 81) and at the PEEP level associated with improved dynamic compliance (median OR 33, 95% CrI 5, 898). Administration of pNMBA to patients with refractory excessive effort was well-tolerated and effectively achieved LDP targets.ConclusionRespiratory effort is frequently absent under deep sedation but becomes excessive when spontaneous breathing is permitted in patients with moderate or severe AHRF. Systematically titrating ventilation and sedation can optimize respiratory effort for lung and diaphragm protection in most patients. VV-ECMO can greatly facilitate the delivery of a LDP strategy.Trial registrationThis trial was registered in Clinicaltrials.gov in August 2018 (NCT03612583).

Project description:ObjectiveTo compare the effectiveness of early high-flow nasal cannula (HFNC) and low-flow oxygen support (LFOS) in children under 5 years with acute hypoxemic respiratory failure (AHRF) due to severe community-acquired pneumonia in low-middle-income countries.MethodsAn open-label randomized clinical trial enrolled children aged 2-59 months with AHRF due to severe community-acquired pneumonia and randomized into HFNC and LFOS. In the LFOS group, the patient received cold wall oxygen humidified by bubbling through sterile water administered through simple nasal prongs at a fixed flow rate of 2 L/min. In the HFNC group, the patient received humidified, heated (37 °C), high-flow oxygen at a flow rate assigned based on weight range, with a titratable oxygen fraction. The primary outcome was treatment failure in 72 h (escalating the respiratory support method using any modality other than primary intervention).ResultsData was analyzed intention-to-treat (HFNC = 124; LFOS = 120). Median (IQR) age was 12 (6-20) and 11 (6-27) months, respectively. Treatment failure occurred in a significantly lower proportion in the HFNC group (7.3%, n = 9/124) as compared to the LFOS group (20%, n = 24/120) (relative risk = 0.36, 95% CI 0.18 to 0.75; p = 0.004; adjusted hazard ratio 0.34, 95% CI 0.16 to 0.73; p = 0.006). The intubation rate was significantly lower in the HFNC group (7.3%, n = 9/124 vs. 16.7%, n = 20/120; relative risk = 0.44, 95% CI 0.21 to 0.92, p = 0.023). There were no significant differences noted in other secondary outcomes. No mortality occurred.ConclusionHigh-flow nasal cannula oxygen therapy used as early respiratory support in children under 5 years with acute hypoxemic respiratory failure due to severe community-acquired pneumonia was associated with significantly lower treatment failure compared with standard low-flow oxygen support.Trial registrationCTRI/2016/04/006788. Registered 01 April 2016, https://ctri.nic.in/Clinicaltrials/advsearch.php.Supplementary informationThe online version contains supplementary material available at 10.1007/s44253-024-00031-8.

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