Low Tidal Volume Ventilation Linked to Lower Mortality in Acute Brain Injury

Among patients with acute brain injury (ABI) — who predominantly do not have acute respiratory distress syndrome (ARDS) — low tidal volume ventilation (LTVV) during the initial 7 days of invasive mechanical ventilation (IMV) was associated with reduced intensive care unit (ICU) mortality up to 60 days, according to study findings published in Chest.

Researchers explored the association between LTVV and mortality in mechanically ventilated patients with ABI via a secondary analysis of the prospective, observational Extubation Strategies in Neuro-Intensive Care Unit Patients and Associations With Outcome (ENIO) trial (ClinicalTrials.gov Identifier: NCT03400904). Trial participants comprised patients at least 18 years of age with ABI from 73 ICUs in 18 countries between June 2018 and November 2020. All participants received invasive ventilation for at least 24 hours.

The exposure in the current analysis was LTVV, which was regarded as tidal volume (V_T)of less than or equal to 8 milliliters per kilogram of predicted body weight (mL/kg PBW), and the comparator was a V_T of more than 8 mL/kg PBW. The exposure was assessed on days 1, 3, and 7 from mechanical ventilation initiation. ICU mortality was the primary endpoint.

The analysis included 1510 patients (mean [SD] age, 52 [18] years; 34.0% female). The most common ABI etiologies were traumatic brain injury (n=726; 48.1%) and intracranial hemorrhage (n=521; 34.5%). The mean follow-up was 15 (13) days.

The mean V_T for the LTVV and control groups, respectively, was 6.8 (0.7) mL/kg and 9.0 (1.0) mL/kg on day 1; 6.7 (0.7) mL/kg and 9.3 (1.2) mL/kg on day 3; and 6.8 (0.8) mL/kg and 9.2 (1.2) mL/kg on day 7.

A total of 122 patients (8.1%) died by day 60. In addition, 1185 patients (78.5%) were censored, of whom 137 (9.2%) developed ARDS in the ICU and the others were discharged from the ICU before 60 days.

The cumulative mortality incidence at 60 days in the pseudo-population of patients who received LTVV during the first 7 days of mechanical ventilation was 40.2% (95% CI, 19.2%-61.1%) vs 59.7% (95% CI, 44.0%-75.4%) in those who received V_T more than 8 mL/kg PBW, according to the adjusted analyses. The marginal hazard ratio (HR) for mortality was 0.54 (95% CI, 0.33-0.88). Point estimates for the other subgroups were similar to the main analysis, although wide confidence intervals occurred.

For LTVV assessed with lower thresholds for V_T, the association with 60-day mortality was indeterminate for all thresholds with wide confidence intervals. In analysis with a negative control outcome, LTVV was not associated with nosocomial ventilator-associated pneumonia (HR, 1.14; 95% CI, 0.72-1.81).

Among several limitations, the primary outcome is based on mortality in a pseudo-population in which all patients remained in the ICU up to 60 days and did not develop ARDS. In addition, unmeasured confounding is likely present, and some subgroup and sensitivity analyses had wide confidence intervals.

“[W]e found that LTVV with V_T≤8 mL/kg PBW over 7 days was associated with lower ICU mortality up to 60 days in patients with ABI, compared to V_T>8 mL/kg PBW,” the study authors stated. However, they added, “When using alternate V_T thresholds below 8m L/kg PBW to define LTVV, the association between ventilatory strategy and mortality was less clear. Taken together, these results cautiously support a clinical strategy limiting exposure to high V_T (>8 mL/kg PBW) in patients with ABI.”

Disclosure: Some 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.

This article originally appeared on Pulmonology Advisor