Age influences on Propofol estimated brain concentration and entropy during maintenance and at return of consciousness during total intravenous anesthesia with target-controlled infusion in unparalyzed patients: An observational prospective trial

PURPOSE: Aging affects pharmacodynamics/pharmacokinetics of anesthetics, but age effects on Entropy-guided total intravenous anesthesia with target-controlled infusions (TIVA-TCI) are not fully characterized. We compared aging effects on effective estimated brain concentration of Propofol (CeP) during TIVA-TCI Entropy-guided anesthesia, without neuromuscular blockade (NMB). METHODS: We performed an observational, prospective, single-center study enrolling 75 adult women undergoing Entropy-guided Propofol-Remifentanil TIVA-TCI for breast surgery. Primary endpoint was the relationship between age and CeP at maintenance of anesthesia (MA) during Entropy-guided anesthesia. Secondary endpoints were relationships between age and CeP at arousal reaction (AR), return of consciousness (ROC) and explicit recall evenience. We calculated a linear model to evaluate the age’s impact on observational variable and performed pairwise tests to compare old (≥65 years, n = 50) and young (<65 years, n = 25) patients or patients with and without an AR. RESULTS: We did not observe age-related differences in CeP during MA, but CeP significantly (p = 0,01) decreased with age at ROC. Entropy values during MA increased with age and were significantly higher in the elderly (RE: median 56[IQR49.3–61] vs 47.5[42–52.5],p = 0.001; SE: 51.6[45–55.5] vs 44[IQR40-50],p = 0.005). 18 patients had an AR, having higher maximum RE (92.5[78–96.3] vs 65[56.5–80.5],p<0.001), SE (79[64.8–84] vs 61[52.5–69],p = 0.03, RE-SE (12.5[9.5–16.5] vs 6 [3–9],p<0.001. CONCLUSION: Older age was associated with lower CeP at ROC, but not during MA in unparalysed patients undergoing breast surgery. Although RE and SE during MA, at comparable CeP, were higher in the elderly, Entropy, and in particular an increasing RE-SE, is a reliable index to detect an AR.