Very Low Driving Pressure Ventilation Is Safe in Patients on ECMO for ARDS

Patients with COVID-19 acute respiratory distress syndrome (ARDS) had no significant biomarker changes with decreased driving pressure (DP) or tidal volume (V_t) within the first 24 hours after extracorporeal membrane oxygenation (ECMO), according to study findings published in the Journal of Cardiothoracic and Vascular Anesthesia.

Researchers sought to test the hypothesis that decreasing lung stretch with very low driving pressure ventilation (V-LDPV) would decrease blood biomarkers of inflammation and lung injury among patients with ARDS on ECMO. Such biomarkers include interleukin-6 (IL-6), interleukin-8 (IL-8), and soluble receptor for advanced glycation end products (sRAGE).

The prospective cohort study enrolled patients from March 1 to November 1, 2020. Eligible participants were older than18 years of age, had plans to start venovenous ECMO support, and had severe ARDS as defined by the Berlin criteria and mechanical ventilation.

Plasma biomarkers were measured at multiple timepoints: (1) pre-ECMO with low tidal volume ventilation (LTVV); (2) post-ECMO with LTVV; (3) post-ECMO with LDPV; (4) post-ECMO after 2 hours of V-LDPV (main intervention); and (5) post-ECMO 2 hours after returning to LDPV from V-LDPV (main intervention).

The primary outcome was the change in plasma IL-6, IL-8, and sRAGE between LDPV and V-LDPV.

A total of 26 participants were enrolled, with 21 (mean [SD] age, 51 [9.7] years; 80.9% male) undergoing the V-LDPV intervention. All participants had ARDS owing to SARS-CoV-2. Of the 21 patients who underwent the V-LDPV protocol, 9 (43%) survived.

Among the group of 21 participants, the mean (SD) V_t from LDPV to V-LDPV and return to LDPV was 3.4 (2.6) to 2.7 (3.2) to 4.0 (2.9) mL/kg predicted body weight (PBW) (P =.075 from LDPV to V-LDPV; P <.001 from V-LDPV back to LDPV).

Of the group, 4 patients were on neuromuscular blockade (NMB) during V-LDPV and did not have spontaneous respirations with esophageal manometry changes and respiratory rate. In addition, 5 participants who were not on NMB had no evidence of spontaneous respiration. The V_t of these 9 patients significantly changed from LDPV to V-LDPV (P < .001), and from V-LDPV to LDPV (P < .001) with V_t of 1.9 (0.5), 0.1 (0.2), and 2.0 (0.7) mL/kg PBW, respectively.

Spontaneous respirations occurred in 12 patients (57%). The V_t in this group did not significantly change from LDPV to V-LDPV (P =.481) and from V-LDPV to LDPV (P =.065), with V_t of 4.5 (3.1) to 4.7 (3.1) to 5.6 (2.9) mL/kg PBW.

No significant changes were observed in safety parameters such as mean arterial pressure, heart rate, pulse oximetry, norepinephrine equivalent dose, ECMO circuit blood flow rate, and ECMO sweep gas flow rate.

No significant changes were found in sRAGE, IL-6, and IL-8 from LDPV to V-LDPV and back to LDPV. No significant association was observed between changes in V_t and sRAGE, IL-6, and IL-8 from LTVV to LDPV and from LDPV to V-LDPV.

Study limitations include the single-center design and modest sample size. In addition, participants exclusively had ARDS owing to COVID-19, and transpulmonary pressure was measured once during the protocol. Furthermore, the study was not powered to detect clinical outcomes such as mortality, and the intervention was relatively brief.

“V-LDPV is feasible and safe for patients on ECMO for ARDS,” stated the investigators. “However, V_t was not uniformly reduced by DP adjustments alone due to spontaneous respiratory efforts. We did not find that changes in DP or V_t correlated with ARDS biomarker levels, within the relatively modest (but typical) V_t studied. Our results suggest that, for patients on ECMO, additional sedation (if effective) and/or NMB might be needed to maintain low V_t that are considered protective.”

Disclosure: One of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.