Nociception Level Index-Guided Intraoperative Opioids in Patients With a Combination of General and Regional Anesthesia

Modern general anesthesia aims to treat nociception induced by surgical stimulation while avoiding an overdose of opioid analgesics and reducing side effects of opioid administration.

Underdosing of opioids during surgery can lead to nociception with increased sympathetic tone, elevated levels of stress hormones, unintended patient movement as well as increased postoperative pain. On the other hand, overdosing of opioids can lead to negative side effects such as nausea and vomiting, arterial hypotension, immunosuppression, prolonged recovery times, postoperative delirium and an increase in postoperative pain by opioid-induced hyperalgesia. Anesthesiologists therefore aim to strike the balance between an effective and long-lasting perioperative anesthesia/analgesia, and keeping the intra- and postoperative opioid dosage as high as needed, but as low as possible to reduce adverse effects. An alternative approach to the intraoperative administration of high-potency opioids for achieving antinociception during surgery is combining general anesthesia with regional anesthesia. By combining the two, the anesthesiologists aim to reduce intraoperative and postoperative opioid administration without compromising reflex control of the autonomous nervous system, immobility of the surgical site without patients' defensive movements, a pain-free awakening after surgery and a pain-free postoperative recovery.

Critically, the quality of regional anesthesia cannot be assessed during general anesthesia by the anesthesiologist, and patients cannot express their pain themselves. Therefore, anesthesiologists tend to administer a certain calculated opioid dose during the operation. Whether this calculated opioid administration is essential for a sufficient anesthesia or is an unnecessary overdose cannot be assessed by the anesthesiologist. To this day, there has been no measurement tool that could estimate the effectiveness of regional anesthesia and the absence of nociception during general anesthesia combined with regional anesthesia.

In recent years, different monitoring devices estimating the effect of nociception during unconsciousness have become commercially available. Such monitoring devices should help physicians to choose the right dose of opioid analgesics during general anesthesia with nociception indices. Among those, the Nociception Level Index (NOL) developed by Medasense Biometrics Ltd, Ramat Yishai, Israel is one of the most promising nociception indices regarding a possible improvement of postoperative patient recovery. This commercially available nociception index has been developed for guiding intraoperative sufentanil administration, has received CE certification for the EU area and an approval by the FDA. The NOL is based on the four physiological parameters heart rate variability, pulse plethysmographic amplitude, skin conductance and skin temperature, which are all measured with a non-invasive finger sensor. A proprietary algorithm generates the NOL from the changes in the four parameters over time using a non-linear random forest regression method through machine learning.

The dimensionless index is presented on a scale from 0 (low sympathetic tone) to 100 (high sympathetic tone) caused by nociception during surgery. According to the manufacturer, a value above 25 indicates a clinically relevant nociceptive response to noxious stimuli while a value below 10 during an operation lasting for more than 2 minutes indicates excessively high analgesia.