Favorable Neurocognitive Outcome with Low Tidal Volume Ventilation after Cardiac Arrest

Abstract

Rationale: Neurocognitive outcome after out-of-hospital cardiac arrest (OHCA) is often poor, even when initial resuscitation succeeds. Lower tidal volumes (Vts) attenuate extrapulmonary organ injury in other disease states and are neuroprotective in preclinical models of critical illness.

Objective: To evaluate the association between Vt and neurocognitive outcome after OHCA.

Methods: We performed a propensity-adjusted analysis of a two-center retrospective cohort of patients experiencing OHCA who received mechanical ventilation for at least the first 48 hours of hospitalization. Vt was calculated as the time-weighted average over the first 48 hours, in milliliters per kilogram of predicted body weight (PBW). The primary endpoint was favorable neurocognitive outcome (cerebral performance category of 1 or 2) at discharge.

Measurements and main results: Of 256 included patients, 38% received time-weighted average Vt greater than 8 ml/kg PBW during the first 48 hours. Lower Vt was independently associated with favorable neurocognitive outcome in propensity-adjusted analysis (odds ratio, 1.61; 95% confidence interval [CI], 1.13-2.28 per 1-ml/kg PBW decrease in Vt; P = 0.008). This finding was robust to several sensitivity analyses. Lower Vt also was associated with more ventilator-free days (β = 1.78; 95% CI, 0.39-3.16 per 1-ml/kg PBW decrease; P = 0.012) and shock-free days (β = 1.31; 95% CI, 0.10-2.51; P = 0.034). Vt was not associated with hypercapnia (P = 1.00). Although the propensity score incorporated several biologically relevant covariates, only height, weight, and admitting hospital were independent predictors of Vt less than or equal to 8 ml/kg PBW.

Conclusions: Lower Vt after OHCA is independently associated with favorable neurocognitive outcome, more ventilator-free days, and more shock-free days. These findings suggest a role for low-Vt ventilation after cardiac arrest.

Keywords: acute lung injury; cardiac arrest; cerebral ischemia; out-of-hospital cardiac arrest; ventilator-induced lung injury.

Figure 1.

Study flow diagram. Of 579 patients with out-of-hospital cardiac arrest (OHCA), 256 were included in the main analyses. Of these, 194 patients (97 pairs) were included in a sensitivity analysis of patients matched by propensity to receive low Vt (≤8 ml/kg predicted body weight [PBW]). APRV = airway pressure release ventilation; ECMO = extracorporeal membrane oxygenation.

Figure 2.

Vt and neurocognitive outcome after out-of-hospital cardiac arrest. Sensitivity analyses performed for primary endpoint, favorable neurocognitive outcome at hospital discharge, to determine whether results were dependent on method of covariate adjustment. Odds ratios represent odds of favorable versus unfavorable neurocognitive outcome (cerebral performance category 1–2 vs. 3–5) per 1-ml/kg predicted body weight (PBW) decrease in Vt. Additional sensitivity analyses (not shown in figure) yielded similar results with Vt reentered as a binary variable and with use of ordinal logistic regression to model cerebral performance category as an ordinal outcome. *Indicates prespecified primary outcome analysis. CI  = confidence interval.

Figure 3.

Probability of discharge with favorable neurocognitive outcome through Day 28. Kaplan-Meier estimates stratified according to time-weighted average Vt received during the first 48 hours of admission. (A) Entire study cohort (n = 256), unadjusted analysis. (B) Cohort matched by propensity for receiving low-Vt ventilation (n = 194). PBW = predicted body weight.

Figure 4.

Vt and secondary outcomes. Effect estimates with 95% confidence intervals (CI) for secondary outcomes from linear regression models, propensity score–adjusted analyses. Effect estimate refers to the change in the outcome variable per 1-ml/kg predicted body weight (PBW) decrease in tidal volume. ICU = intensive care unit.