Correlation between incremental remifentanil doses and the Nociception Level (NOL) index response after intraoperative noxious stimuli.

BACKGROUND: The Pain Monitoring Device (PMD) monitor (Medasense Biometrics Ltd., Ramat Gan, Israel) uses the Nociception Level (NOL) index, a multiple parameter-derived index that has recently shown a good sensitivity and specificity to detect noxious stimuli. The aim of this study was to assess the latest version of the device (PMD200TM) on variations of the NOL response after standardized tetanic stimuli to study the correlation between remifentanil doses and NOL. METHODS: Data from 26 patients undergoing midline laparotomy and receiving a desflurane-remifentanil-based anesthetic coupled with low thoracic epidural analgesia were analyzed. A standardized tetanic stimulus was applied to the forearm of the patients at different remifentanil infusion rates. The primary aim was to evaluate the correlation between post-tetanic stimulation NOL values from the PMD200 and remifentanil doses. The NOL index variations after experimental and clinical stimuli were also compared with heart rate (HR), mean arterial pressure (MAP), and Bispectral Index™ (BIS). RESULTS: A correlation between post-tetanic stimulation NOL values and remifentanil doses was found (r = -0.56; 95% confidence interval [CI], -0.70 to -0.44; P < 0.001). The NOL discriminated noxious from non-noxious states with the maximal Youden's index value of the NOL receiver operating characteristic (ROC) curve showing a specificity of 88% (95% CI, 69.0 to 100) and sensitivity of 79.1% (95% CI, 56.2 to 95.5). The area under the NOL ROC curve (AUC, 0.9; 95% CI, 0.84 to 0.95) was significantly different from the other variables (P < 0.001 vs HR; P < 0.001 vs MAP; P < 0.001 vs BIS). CONCLUSIONS: The NOL value after noxious stimulus decreased with incremental remifentanil doses, showing a significant inverse correlation between the NOL index and opioid doses. The sensitivity and specificity of NOL to discriminate between noxious and non-noxious stimuli suggests its interesting potential as a monitor of nociception intensity during anesthesia. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02884778); 27 July, 2016.

Validation of the PMD100 and its NOL Index to detect nociception at different infusion regimen of remifentanil in patients under general anesthesia.

BACKGROUND: The NOL index is based on multiparametric analysis of heart rate (HR), skin conductance, wave plethysmography, and their time derivative. The aim of this study was to evaluate the NOL to detect standardized nociceptive stimuli with various remifentanil dosages under general anesthesia. METHODS: A prospective, observational study at a single center (NCT02602379) included 40 ASA I to III patients undergoing laparotomy under remifentanil-desflurane anesthesia with epidural analgesia. A tetanic stimulation was applied (forearm) at remifentanil intravenous (IV) infusion of 0.005, 0.05, 0.1, and 0.15 µg/kg/min. NOL and its variations were compared with other parameters namely heart rate, mean arterial pressure, Bispectral Index, and Analgesia Nociception Index (ANI). Receiver operating characteristic (ROC) curves were plotted to assess the response to both intubation and standardized stimulus under remifentanil infusion of 0.005 µg/kg/min. RESULTS: The post-stimulation NOL values at remifentanil doses of 0.005, 0.05, 0.1 and 0.15 µg/kg/min (39 [23-55], 15 [7-30], 8 [4-14] and 8.5 [4-15]) were significantly higher than pre-stimulation counterparts (P<0.0001). For all other parameters, there was also significant difference between pre- and post-stimulation values at all remifentanil dosages (P<0.0001). Area under the ROC curve (AUC) for the NOL during standardized stimulation was larger than for all other parameters at the exception of ANI (P=0.94). The AUC of NOL for nociception during tracheal intubation was greater (0.93 vs. 0.84 and 0.64 for ANI and HR, respectively). CONCLUSIONS: NOL monitoring is a promising index to assess the level of nociception in patients under general anesthesia.