“Low-” versus “high”-frequency oscillation and right ventricular function in ARDS. A randomized crossover study

BACKGROUND: Recent, large trials of high-frequency oscillation (HFO) versus conventional ventilation (CV) in acute respiratory distress syndrome (ARDS) reported negative results. This could be explained by an HFO-induced right ventricular (RV) dysfunction/failure due to high intrathoracic pressures and hypercapnia. We hypothesized that HFO strategies aimed at averting/attenuating hypercapnia, such as “low-frequency” (i.e., 4 Hz) HFO and 4-Hz HFO with tracheal-gas insufflation (HFO-TGI), may result in an improved RV function relative to “high-frequency” (i.e., 7 Hz) HFO (which may promote hypercapnia) and similar RV function relative to lung protective CV. METHODS: We studied 17 patients with moderate-to-severe ARDS [PaO(2)-to-inspiratory O(2) fraction ratio (PaO(2)/FiO(2)) < 150]. RV function was assessed by transesophageal echocardiography (TEE). Patients received 60 min of CV for TEE-guided, positive end-expiratory pressure (PEEP) “optimization” and subsequent stabilization; 60 min of 4-Hz HFO for “study mean airway pressure (mPaw)” titration to peripheral oxygen saturation ≥ 95%, without worsening RV function as assessed by TEE; 60 min of each tested HFO strategy in random order; and another 60 min of CV using the pre-HFO, TEE-guided PEEP setting. Study measurements (i.e., gas exchange, hemodynamics, and TEE data) were obtained over the last 10 min of pre-HFO CV, of each one of the three tested HFO strategies, and of post-HFO CV. RESULTS: The mean “study HFO mPaw” was 8–10 cmH(2)O higher relative to pre-HFO CV. Seven-Hz HFO versus 4-Hz HFO and 4-Hz HFO-TGI resulted in higher mean ± SD right-to-left ventricular end-diastolic area ratio (RVEDA/LVEDA) (0.64 ± 0.15 versus 0.56 ± 0.14 and 0.52 ± 0.10, respectively, both p < 0.05). Higher diastolic/systolic eccentricity indexes (1.33 ± 0.19/1.42 ± 0.17 versus 1.21 ± 0.10/1.26 ± 0.10 and 1.17 ± 0.11/1.17 ± 0.13, respectively, all p < 0.05). Seven-Hz HFO resulted in 18–28% higher PaCO(2) relative to all other ventilatory strategies (all p < 0.05). Four-Hz HFO-TGI versus pre-HFO CV resulted in 15% lower RVEDA/LVEDA, and 7%/10% lower diastolic/systolic eccentricity indexes (all p < 0.05). Mean PaO(2)/FiO(2) improved by 77–80% during HFO strategies versus CV (all p < 0.05). Mean cardiac index varied by ≤ 10% among strategies. Percent changes in PaCO(2) among strategies were predictive of concurrent percent changes in measures of RV function (R(2) = 0.21–0.43). CONCLUSIONS: In moderate-to-severe ARDS, “short-term” 4-Hz HFO strategies resulted in better RV function versus 7-Hz HFO, partly attributable to improved PaCO(2) control, and similar or improved RV function versus CV. TRIAL REGISTRATION: This study was registered 40 days prior to the enrollment of the first patient at ClinicalTrials.gov, ID no. NCT02027129, Principal Investigator Spyros D. Mentzelopoulos, date of registration January 3, 2014. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40560-018-0327-3) contains supplementary material, which is available to authorized users.