**1. Introduction**

First described in the mid-20th century, cognitive dysfunction following anesthesia and surgery is a complication that can have a significant impact on patients, leading to unfavorable outcomes [1]. Postoperative cognitive dysfunction (POCD) is described as a decline of the intellectual functions and processes (both basic and higher executive skills) that develops after surgery [2]. Although recognized as a transient decline of cognitive function, POCD can persist for weeks, months, or more. POCD also interferes with patients' psychological status, long-term outcome, mortality, and hospital discharge [3–5].

Postoperative cognitive decline occurs more frequently in the elderly population, with a higher incidence in patients older than 60 years irrespective of the type of anesthesia and

**Citation:** Cotae, A.-M.; ¸Tigli¸s, M.; Cobilinschi, C.; B ˘aetu, A.E.; Iacob, D.M.; Grin¸tescu, I.M. The Impact of Monitoring Depth of Anesthesia and Nociception on Postoperative Cognitive Function in Adult Multiple Trauma Patients. *Medicina* **2021**, *57*, 408. https://doi.org/10.3390/ medicina57050408

Academic Editor: Stefania Mondello

Received: 10 March 2021 Accepted: 20 April 2021 Published: 23 April 2021

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**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

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surgery. Despite the fact that studies assessing cognitive impairment have been primarily centered on the study of older patients, there is a general agreemen<sup>t</sup> that POCD is more likely to occur after major surgery [5,6]. Although this type of cognitive dysfunction is considered multifactorial, it remains difficult to determine whether its occurrence is a result of patient-, surgical-, or anesthesia-related factors [7]. Several risk factors have been suggested to be involved in the pathophysiology of cognitive dysfunction, such as inflammatory cytokines, pain, preoperative impairment in neurocognitive function, metabolic disturbances, duration/type of surgery, hypoxemia, old age, and the use of certain anesthetics (sedation medication or different volatile anesthetic agents) [5–8].

Fortunately, several screening tests are available to establish cognitive disorders. Among these, one stands out for being easily performed without supplemental training. The Neelon and Champagne (NEECHAM) Confusion Scale was developed not only to identify postoperative delirium but also to classify patients as "early to mild confused ", "at risk", or "normal " [9,10]. A score between 0 and 24 points is conclusive for the presence of at least one cognitive impairment. The scale has acceptable sensitivity, specificity, and predictive values when compared to the CAM-ICU [11].

This recent development encourages us to use electroencephalography (EEG) monitoring to assess the depth of anesthesia. Using neuromonitoring during anesthetic delivery can reduce the risk for postoperative cognitive side effects [12]. Among the anesthesia monitors currently approved to assess the depth of anesthesia, the entropy monitor proves to be one of the most reliable. The entropy device is capable of acquiring not only EEG signals but also frontal electromyography data, transforming them into two values: State and response entropy. The entropy device then displays state and response entropy as numerical values, denoting the depth of anesthesia. State entropy and response entropy are given indices between 0–91 and 0–100, respectively, ranging from complete suppression of cortical neuronal activity to an awake-state EEG [13].

As we have already mentioned, another important element in developing POCD is pain. In order to monitor intraoperative nociceptive stimulation and antinociceptive drug effects, different tools have been proposed over the years. Among them, the Surgical Pleth Index (SPI) has received recognition after several studies reported a better outcome in comparison to conventional analgesia. The Surgical Pleth Index module is designed to acquire and process the plethysmograph pulse wave and heartbeat frequency. The parameter has a range of value between 0 and 100. Although there is little to no validation of a specific cut-off value, previous studies have recommended a target value of SPI ≤ 50 [14,15].

The aim of this study was to reduce the incidence of POCD in the first 72 h by assessing anesthetic depth using entropy and nociception through the Surgical Pleth index (SPI) during emergency surgery.

#### **2. Materials and Methods**

#### *2.1. Study Design*

This prospective randomized study was carried out in the Anaesthesia and Intensive Care Clinic, Clinical Emergency Hospital of Bucharest, between August 2018 and January 2019. All the procedures performed during this study were in accordance with the Declaration of Helsinki.

The study was approved by the Research Ethical Committee of our hospital (registration number 2100/2021), and all the patients provided written informed consent. Patients were considered eligible for the study if they were over 18 years old, undergoing emergency noncardiac surgery expected to last at least 2 h, and American Society of Anesthesiologists (ASA) physical status II, III, or IV. The surgical procedures included abdominal (splenectomy, splenorrhapy, hepatorrhapy, hemicolectomy, phrenoraphy) and orthopedic (femoral osteosynthesis, tibial osteosynthesis, humeral osteosynthesis) surgery. Exclusion criteria were neurotrauma, chronic use of psychoactive substances or alcohol, impaired preoperative cognitive function pre-existing psychopathological symptoms, neurological deficits, or expected surgery time less than 2 h. From the collection data process,

we excluded patients intubated prior to the surgical procedure and those who remained intubated at the end of the surgical procedure. The patients were consecutively assigned into 2 study groups. In the first group, anesthesia was provided under standard monitoring (SMG): 5-lead electrocardiogram, noninvasive arterial pressure, pulse oximetry, temperature and end-tidal carbon dioxide concentration. In the second group, apart from standard monitoring, entropy and SPI data were allowed to be included into the managemen<sup>t</sup> of anesthesia (ESMG).
