Title:
Impact of sedation and organ failure on continuous heart and respiratory rate variability monitoring in critically ill patients: a pilot study.

Abstract:
Our aim is to better characterize the impact of sedation and its interruption on continuously monitored heart rate variability and respiratory rate variability in critically ill patients. We aim to explore whether sedation reduces heart rate variability and respiratory rate variability in critically ill patients and whether the extent of reduction depends on degree of organ dysfunction.
Prospective observational pilot study.
Intensive care unit in tertiary care teaching hospital.
Thirty-three critically ill adult patients experiencing respiratory and/or cardiac failure.
Electrocardiogram and end-tidal capnography waveform capture were initiated from admission or intubation, respectively, and continued to intensive care unit discharge or a maximum of 14 d.
All patient days with a sedation interruption (defined as cessation of a continuous infusion of sedation agent) were identified. Mean heart rate variability and respiratory rate variability were computed over two periods: 4 hrs directly prior to the sedation interruption, and the duration of sedation interruption (median: 1 hr 45 mins, interquartile range: 4 hrs 15 mins or max 4 hrs). Severity of organ dysfunction was assessed through multiple organ dysfunction syndrome scores, and sedative agents were recorded for each sedation interruption. Multiple organ dysfunction syndrome levels were defined as low (0-2), medium (3-4), and high (> 4). Variability before and during sedation interruption was compared and analyzed across multiple organ dysfunction syndrome levels and sedative types. Our results suggest that both heart rate variability and respiratory rate variability increased during sedation interruption (p < 0.05 for coefficient of variation). Patients with low and medium multiple organ dysfunction syndrome experienced greater increase in heart rate variability during sedation interruption (p < 0.05 for coefficient of variation), compared to patients with high multiple organ dysfunction syndrome, who failed to mount a significant increase in heart rate variability when sedation was stopped. Similarly, sedation interruption led to increased respiratory rate variability for low multiple organ dysfunction syndrome patients (p < 0.05 for SD), but in contrast, a further deterioration in respiratory rate variability occurred in the high multiple organ dysfunction syndrome patients. All trends persisted when controlling for sedative agents.
Interruption of sedation allows for uncovering a greater restoration of heart rate variability and respiratory rate variability in patients with low organ failure. The further reduction in respiratory variability during the elimination of sedation in patients with high multiple organ dysfunction syndrome suggests a differential response and benefit from sedation interruption, and merits further investigation. As reduced variability correlates with severity of illness, and need for sedation depends on organ failure, variability monitoring may offer a dynamic measure of a variable response to the benefit, timing, and duration of sedation interruption.