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.

JianJun Yang,Federico Linassi,Matthias Kreuzer,Michele Carron,Eleonora Maran,Antonio Farnia,Paolo Zanatta,Paolo Navalesi

doi:10.1371/journal.pone.0244145

Abstract

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). 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. 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. 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.

Highlights

Total intravenous anesthesia with target-controlled infusions (TIVA-TCI) allows anesthetists to achieve a stable plasma or estimated brain concentration of Propofol and Remifentanil (CeP and Effective estimated brain concentration of remifentanil (CeR), respectively) and to promptly respond to signs of inappropriate anesthetic/analgesic plans, being considered the “ideal” approach by some clinicians [1]
Older age was associated with lower CeP at return of consciousness (ROC), but not during maintenance of anesthesia (MA) in unparalysed patients undergoing breast surgery
CeP at loss of consciousness (LOC) and return of consciousness (ROC) during TIVA-TCI are lower in the elderly than in younger patients [6,7]

Summary

Introduction

Total intravenous anesthesia with target-controlled infusions (TIVA-TCI) allows anesthetists to achieve a stable plasma or estimated brain concentration of Propofol and Remifentanil (CeP and CeR, respectively) and to promptly respond to signs of inappropriate anesthetic/analgesic plans, being considered the “ideal” approach by some clinicians [1]. The Entropy module calculating the State (SE) and Response Entropy (RE) (Entropy Module, GE Healthcare, Chicago, IL, USA) [9] is one of these devices that translates the EEG activity into dimensionless indices inversely related to the anesthetic level by using specially designed algorithms [9]. The use of these indices seems to decrease the risk of Post-Operative Cognitive Dysfunction (POCD) or intraoperative awareness by helping to avoid excessively deep or light levels of anesthesia [10,11], but their usefulness for these purposes is matter of controversial discussion [12,13,14,15]. Previous results describe an influence of age on these indices [16,17], because aging changes intraoperative EEG features [18,19]

Objectives

Methods

Conclusion