Cardio-respiratory autonomic responses to nociceptive stimuli in patients with disorders of consciousness

Abstract

The autonomic response to pain might discriminate among consciousness disorders. Therefore, aim of this study was to describe differences between minimally conscious state (MCS) and unresponsive wakefulness syndrome (UWS) patients in their autonomic response to a nociceptive stimulus. ECG, respiration, finger blood pressure (BP) and total peripheral resistances (TPR) were continuously recorded before, during and after a standardized noxious stimulus in 20 adult brain-injured patients, 14 in UWS and 6 in MCS. Occurrence of fast autonomic responses synchronous with the stimulus was detected by visual inspection of the tracings; short-term (<20 s) and long-term (between 20s and 50 s from the stimulus) responses were evaluated by beat-by-beat quantitative analysis. The noxious stimulus elicited fast responses in both groups, but only MCS patients showed a significant short-term response in TPR and long-term response in HR. Thus, short- and long-term cardiovascular responses to pain might integrate neuro-behavioural assessments to discriminate between MCS and UWS.

Fig 1. Examples of 2-minute data segments.

Beat-by-beat series of SBP, DBP (upper panels), and RRI (central panels) and respiratory movements of the thorax (lower panels) in a patient classified as not-responder to the noxious stimulus (column A), as responder (column B), and as not-responder with periodic breathing (column C). The nociceptive stimulus, indicated by a vertical line and the letter “s”, was delivered in the middle of each time window (t = 60 s).

Fig 2. Reference and response periods for short-term and long-term analysis.

Time series are split into consecutive blocks of 10 s; short- and long-term autonomic responses are quantified as increments from “reference” to “response” periods. The arrows indicate the application of the stimulus, with its 5-s duration highlighted by the red bar. References are the 10-s period (short-term) or 30-s period (long-term) preceding the stimulus; response periods have the same length of reference periods and start few seconds after the cessation of the stimulus (short-term response) or after the period selected for the short-term analysis (long-term response). Short-term analysis also quantifies changes during the “stimulus” condition; long-term analysis also consider a 90-s baseline period for evaluating if the operators interacting with the patient before the administration of the stimulus may have influenced the variables measured in the reference period.

Fig 3. Frequency distribution of NCS scores.

Frequency distribution is shown for the MCS (left histogram) and UWS (right histogram) groups; the arrows show the median values of each distribution; the “**” indicates a statistically significant difference between distributions at p<0.01 (Mann Whitney U test).

Fig 4. Short–term analysis of the noxious stimulus in MCS and UWS patients.

Grey bars: increments from “reference” to “stimulus” condition; red bars: increments from “reference” to “response” condition: values as mean ± sem; the * indicates increments significantly different from 0, the # indicates significant differences between “stimulus” and “response” increments (p<0.05).

Fig 5. HR profile around the noxious stimulus in MCS and UWS patients.

Data are mean and sem. The arrow pointing at t = 0 indicates the instant of stimulus application; the flag on the arrow indicates the duration of the stimulus (5 s); the * mark differences vs. baseline significant at p<0.05.

Fig 6. SBP, DBP, SV and TPR profiles around the noxious stimulus.

Data as mean and sem; the arrow indicates the stimulus application. No differences vs. baseline were significant at p<0.05.

Fig 7. Correlation between NCS score and autonomic indices of short-term and long–term response to nociception stimulus.

Left: short-term response in TPR; right: long-term response in HR.