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The results of this study indicate that postoperative pain is associated with a decreased high-frequency HRV in full-term newborn infants. Our findings suggest that HRV could be used as an indicator to assess prolonged pain in the newborn infants.

Continuous Analgesia / Nociception balance evaluation during general anesthesia could be of precious help for the optimization of analgesic drugs delivery, limiting the risk of toxicity due to the use of opioid drugs, limiting the risk of post operative hyper algesia, and, probably, reducing time of recovery after surgical procedure. Heart Rate Variability analysis has been shown in several studies to measure the Autonomic Nervous System tone, which is strongly influenced by anesthetic drugs. Recording RR series during general anesthesia enabled us to observe that the Respiratory Sinus Arrhythmia pattern changed when a surgical stimulation was painful, even though the patient was not conscious. We have previously developed and evaluated a pain / analgesia measurement algorithm based on the magnitude analysis of the respiratory patterns on the RR series. In this paper, we present the development of a monitoring device (PhysioDoloris), based on the previously described technology, giving in real time an Analgesia Nociception Index (ANI) which can be used during general anesthesia in order to give to the anesthetist, a complementary tool for optimized drug delivery.

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The analgesia nociception index (ANI) is an online heart rate variability analysis proposed for assessment of the antinociception/nociception balance. In this observational study, we compared ANI with heart rate (HR) and systolic blood pressure (SBP) during various noxious stimuli in anaesthetized patients. 15 adult patients undergoing laparoscopic appendectomy or cholecystectomy were studied. Patients received target controlled infusions of propofol (adjusted to maintain the Bispectral index in the range [40-60]) and remifentanil (with target increase in case of haemodynamic reactivity [increase in HR and/or SBP >20% of baseline]), and cisatracurium. Medical staff was blind to the ANI monitor. ANI and haemodynamic data were recorded at predefined times before and during surgery, including tetanic stimulation of the ulnar nerve before start of surgery. Anaesthesia induction decreased HR and SBP, while high ANI values (88 [17]) were recorded, indicating parasympathetic predominance. In 10 out of 11 patients, tetanic stimulation led to a transient (<5 min) decrease in ANI to 48 (40) whereas HR and SBP did not change. After start of surgery, ANI decreased to 60 (39) and decreased further to 50 (15) after the pneumoperitoneum was inflated, while there was no significant change in HR or SBP. When haemodynamic reactivity occurred, ANI had further decreased to 40 (15). After completion of surgery, ANI returned to 90 (34). ANI seems more sensitive than HR and SBP to moderate nociceptive stimuli in propofol-anaesthetized patients. Whether ANI monitoring may allow preventing haemodynamic reactivity to noxious stimuli remains to be demonstrated.

The optimization of analgesic drugs delivery during general anesthesia (GA) requires to evaluate the pain/analgesia balance. Heart Rate Variability (HRV) analysis has long been shown to measure the autonomic nervous system tone, which is strongly influenced by anesthetic drugs. Power spectrum measurements are widely used to assess HRV low (LF) and high frequency (HF) ranges, related to the sympathetic and parasympathetic systems. We have developed an original graphic measurement technique (EnvTOT) of the ventilatory influence on the RR series. Measurements on simulated RR series showed that the graphic assessment is independent from respiratory rate, while LF and HF spectral measurements are over- and underestimated for respiratory rates lower than 12 cycles min Clinical measurements on 49 patients during GA showed that normalized HF power was strongly related to hemodynamic responsiveness during GA, and was strongly correlated with normalized EnvTOT measurements. A real time computation of the RR series could therefore help medical staff to anticipate hemodynamic responsiveness and the analgesia/nociception balance during GA.

Aim-To analyse the immediate response of heart rate variability (HRV) in response to orthostatic stress in unexplained syncope. Subjects-69 subjects, mean (SD) age 42 (18) years, undergoing 60°head up tilt to evaluate unexplained syncope. Methods-Based on 256 second ECG samples obtained during supine and upright phases, spectral analyses of low (LF) and high frequency (HF) bands were calculated, as well as the LF/HF power ratio, reflecting the sympathovagal balance. All variables were measured just before tilt during the last five minutes of the supine position, during the first five minutes of head up tilt, and just before the end of passive tilt. Results-Symptoms occurred in 42 subjects (vasovagal syncope in 37; psychogenic syncope in five). Resting haemodynamics and HRV indices were similar in subjects with and without syncope. Immediately after assuming the upright posture, adaptation to orthostatism diVered between the two groups in that the LF/HF power ratio decreased by 11% from supine (from 2.7 (1.5) to 2.4 (1.2)) in the positive test group, while it increased by 11.5% (from 2.8 (1.5) to 3.1 (1.7)) in the negative test group (p = 0.02). This was because subjects with a positive test did not have the same increment in LF power with tilting as those with a negative test (11% v 28%, p = 0.04), while HF power did not alter. A decreased LF/HF power ratio persisted throughout head up tilt and was the only variable found to discriminate between subjects with positive and negative test results (p = 0.005, multivariate analysis). During the first five minutes of tilt, a decreased LF/HF power ratio occurred in 33 of 37 subjects in the positive group and three of 27 in the negative group. Thus a decreased LF/HF ratio had 89% sensitivity, 89% specificity, a 92% positive predictive value, and an 86% negative predictive value. Conclusions-Through the LF/HF power ratio, spectral analysis of HRV was highly correlated with head up tilt results. Subjects developing syncope late during continued head up tilt have a decrease in LF/HF ratio immediately after assuming the upright posture, implying that although symptoms have not developed the vasovagal reaction may already have begun. This emphasises the major role of the autonomic nervous system in the genesis of vasovagal (neurally mediated) syncope. (Heart 1999;82:312-318)

ANI measures during propofol anesthesia are coherent with the evolution of the analgesia/nociception balance, although its performance decreases in awake patients. Further clinical validation should focus on demonstrating the benefit of maintaining ANI over 63 during surgery.