Validation of Innovative Techniques for Monitoring Nociception during General Anesthesia: A Clinical Study Using Tetanic and Intracutaneous Electrical Stimulation

Anesthesiology. 2017 Aug;127(2):272-283. doi: 10.1097/ALN.0000000000001670.


Background: This study compares the analgesic indices Analgesia Nociception Index (heart rate variability), Surgical Pleth Index (photoplethysmography), and pupillary dilatation, to heart rate, mean arterial pressure, and bispectral index, with regard to diagnostic accuracy and prediction probability for nociceptive response. The primary endpoint was the correlation between Δ values and the remifentanil dose administered.

Methods: We anesthetized 38 patients with propofol and increasing doses of remifentanil and applied standardized tetanic and intracutaneous electrical painful stimulations on each analgesic level. Baseline and Δ values of the Analgesia Nociception Index, the Surgical Pleth Index, pupillary dilatation, heart rate, mean arterial pressure, and bispectral index and their relation to remifentanil doses were analyzed by receiver operating characteristic curves, prediction probability (PK), and mixed-model analysis.

Results: Under propofol sedation, sensitivity and specificity of the Analgesia Nociception Index (PK = 0.98), the Surgical Pleth Index (PK = 0.87), and pupillary dilatation (PK = 0.98) for detecting both painful stimulations were high compared to heart rate (PK = 0.74), mean arterial pressure (PK = 0.75), and bispectral index (PK = 0.55). Baseline values had limited prediction probability toward the nociceptive response (Analgesia Nociception Index: PK = 0.7; Surgical Pleth Index: PK = 0.63; pupillary dilatation: PK = 0.67; and bispectral index: PK = 0.67). The remifentanil dose had an effect (P < 0.001) on all parameters except for bispectral index (P = 0.216).

Conclusions: The Analgesia Nociception Index, the Surgical Pleth Index, and pupillary dilatation are superior in detecting painful stimulations compared to heart rate and mean arterial pressure but had limited predictive value. These effects are attenuated by increasing dosages of remifentanil. Our data confirm that bispectral index is not a marker of analgesia.

Publication types

  • Validation Study

MeSH terms

  • Anesthesia, General*
  • Anesthetics, Intravenous / pharmacology
  • Arterial Pressure / drug effects
  • Electric Stimulation*
  • Electroencephalography / drug effects
  • Female
  • Heart Rate / drug effects
  • Humans
  • Male
  • Middle Aged
  • Monitoring, Intraoperative / methods*
  • Nociception / drug effects*
  • Piperidines / pharmacology*
  • Pupil / drug effects
  • Remifentanil


  • Anesthetics, Intravenous
  • Piperidines
  • Remifentanil