Discordance Between Respiratory Drive and Sedation Depth in Critically Ill Patients Receiving Mechanical Ventilation

Abstract

Objectives: In mechanically ventilated patients, deep sedation is often assumed to induce "respirolysis," that is, lyse spontaneous respiratory effort, whereas light sedation is often assumed to preserve spontaneous effort. This study was conducted to determine validity of these common assumptions, evaluating the association of respiratory drive with sedation depth and ventilator-free days in acute respiratory failure.

Design: Prospective cohort study.

Setting: Patients were enrolled during 2 month-long periods in 2016-2017 from five ICUs representing medical, surgical, and cardiac specialties at a U.S. academic hospital.

Patients: Eligible patients were critically ill adults receiving invasive ventilation initiated no more than 36 hours before enrollment. Patients with neuromuscular disease compromising respiratory function or expiratory flow limitation were excluded.

Interventions: Respiratory drive was measured via P0.1, the change in airway pressure during a 0.1-second airway occlusion at initiation of patient inspiratory effort, every 12 ± 3 hours for 3 days. Sedation depth was evaluated via the Richmond Agitation-Sedation Scale. Analyses evaluated the association of P0.1 with Richmond Agitation-Sedation Scale (primary outcome) and ventilator-free days.

Measurements and main results: Fifty-six patients undergoing 197 bedside evaluations across five ICUs were included. P0.1 ranged between 0 and 13.3 cm H2O (median [interquartile range], 0.1 cm H2O [0.0-1.3 cm H2O]). P0.1 was not significantly correlated with the Richmond Agitation-Sedation Scale (RSpearman, 0.02; 95% CI, -0.12 to 0.16; p = 0.80). Considering P0.1 terciles (range less than 0.2, 0.2-1.0, and greater than 1.0 cm H2O), patients in the middle tercile had significantly more ventilator-free days than the lowest tercile (incidence rate ratio, 0.78; 95% CI, 0.65-0.93; p < 0.01) or highest tercile (incidence rate ratio, 0.58; 95% CI, 0.48-0.70; p < 0.01).

Conclusions: Sedation depth is not a reliable marker of respiratory drive during critical illness. Respiratory drive can be low, moderate, or high across the range of routinely targeted sedation depth.

Figure 1.. P_0.1 and Richmond Agitation-Sedation Scale (RASS).

Overlaid box-and-whisker and scatter plot. Boxes represent median with interquartile range; whiskers extend 1.5 times the interquartile range beyond the first and third quartiles per the Tukey method. Diamonds represent mean values. Circles indicate individual observations; total of 197 observations were performed and all displayed. P_0.1 values within each RASS level were randomly jittered to facilitate visualization. During the study period, the highest RASS observed was +1.

Figure 2.. Respiratory drive is poorly correlated with sedation depth.

Pearson and Spearman correlations for cross-sectional relationship between P_0.1 and sedation depth assessed via Richmond Agitation-Sedation Scale (RASS). Higher RASS corresponds to increased arousal (lighter sedation depth).

Figure 3.. Both high and low respiratory drive, compared to moderate drive, are associated with fewer ventilator-free days.

(A) Overlaid box-and whisker and scatter plots of all P_0.1 values for each patient; red diamonds represent mean values, and circles indicate values from individual observations. Boxes represent median with interquartile range; whiskers extend 1.5 times the interquartile range beyond the first and third quartiles per the Tukey method. Shaded vertical bars indicate number of ventilator-free days for each patient (secondary Y-axis). Patients are sorted by number of ventilator free days and average P_0.1 value to aid interpretation. (B) Locally estimated scatterplot smoothing (LOESS) regression line with 95% confidence bands for model associating P_0.1 with ventilator-free days.