PJ-008200 Measurements on healthy subjects to design a nociception index

Pain is defined by the International Association for the Study of Pain as “an unpleasant sensory and emotional experience

associated with actual or potential tissue damage, or described in terms of such damage”. Nociception is “the neural process of

encoding noxious stimuli”.

Nociception during surgery can lead to surgically-induced neuropathic pain (SNPP). SNPP has been estimated to occur in 10-

50% of patients. To prevent SNPP, a perioperative strategy would be to continuously block nociception, and for this an objective

measure of nociception is necessary.

In clinical practice it is seldom possible to completely block activation of the nociceptive pathways. When spinal or regional

anesthesia is not possible, the one of the opioid drugs is administered to counteract the nociceptive signals. At present it is very

difficult for clinicians to judge when or if the opioid dose is adequate, and this is a problem because both inadequate and

excessive doses have adverse consequences. In adequate doses of opioids are associated with sympathetic activation and

hemodynamic instability (tachycardia and hypertension), and possibly an increased risk of SNPP. On the other hand excessive

doses are associated with adverse effects such as bradycardia and hypotension, post-operative nausea and vomiting,

generalized itching and constipation. Moreover, excessive doses may be associated with opioid tolerance and opioid-induced

hyperalgesia which can lead to increased post-operative opioid requirements, and eventually a higher incidence of SNPP.

Nociception measurement and management is a quality indicator for hospitals. Monitoring of nociception in the OR could result

in improved patient safety, higher OR throughput, and better patient outcome.

In current clinical practice, anesthesiologists primarily rely on changes in heart rate (HR) and arterial blood pressure (ABP) as a

measure of the balance between nociception and anti-nociception (i.e. the dose of analgesic drugs) during surgery. However,

with this approach some nociceptive responses may be missed.

There is a need for a continuous, objective nociception index especially for sedated unconscious patients who cannot express

their pain levels. There is an increasing number of new nociception/pain/stress indices in the market using a combination of vital

signs, using galvanic skin conductance or brain signals or using a combination of different parameters. However, none of these

technologies is currently better than BP and HR in predicting nociceptive response and there is definitely room for improvement.

In our current study, we aim to use a novel combination of parameters to design a unique nociception index.

Heart rate variability (HRV) is a widely used measure of alterations in sympathetic and parasympathetic autonomic nervous

system activity. HRV has been associated with nociceptive stimuli since many years. More recent studies have underpinned the

potential value of HRV in nociception measurement.

Another physiological response to nociceptive events is an increase in blood pressure. This has been shown for tonic

nociceptive stimuli, as well as short nociceptive stimuli.

Photoplethysmography (PPG) measures local blood volume changes, e.g. at the fingertip. The pre-processing of a patient

monitor removes some of the information in a PPG waveform, which is why we chose a recording method that avoids this. The

PPG waveform consists of a DC component (i.e. low-frequency variations) and an AC component (higher frequency variations).

The AC component has been shown to be relevant for measuring nociception. Various parameters can be derived from the PPG

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waveform, such as amplitude, area under the curve, and rising slope.

Galvanic skin response is a measure that is used to measure stress, and has also been linked to noci

The primary objective is to measure the effect of nociceptive stimuli on features derived from ECG, ABP, PPG, EEG and facial

video recordings, to be used to design an index of nociception. The index of nociception should correlate well with strength of

nociceptive stimulus and subjective NRS score.

The secondary objectives are to:

- Analyse the effect of remifentanil on the correlation between the index of nociception and the stimulus strengths and related

subjective NRS scores (remifentanil is standard in surgery care, is fast acting, and often used in other studies that research

nociception).

- Evaluate the performance of within Philips Research earlier developed vital sign based (i.e. HRV, BP) algorithms.

- Benchmark the index of nociception with indices on the market such as ANI (Analgesia Nociception

Evaluate the performance of the PainChek facial expressions algorithm for pain detection

Patient will receive a standardized pain protocol with and without administration of remifentanil. The pain protocol consists of electrical and thermical pain stimuli and the ice bucket water test.