ORIGINAL ARTICLE
COMPARISON OF THE EFFECTS OF DESFLURANE AND SEVOFLURANE IN AWAKENING AND COGNITIVE FUNCTION AFTER A GENERAL ANESTHESIA

UDK: 616-089.168.1-085.211.015

Ognjanova Simjanovska V1, Shirgoska B2, Donev Lj3, Angjusev D3, Leshi A3

 

1KARIL, TOARILUC, Skopje, Macedonia

2ENT University Clinic, Medical Faculty, “Ss. Cyril and Methodius” University, Skopje

 

Abstract

 

Introduction: The pharmacokinetics of desflurane and sevoflurane favor improved intraoperative control of anesthesia and led to faster postoperative recovery. These anesthetics have a lower blood/ gas coefficient than isoflurane and halothane. The low fat/ gas coefficient and low brain/ blood coefficient of desflurane lead to faster elimination and faster awakening from anesthesia. This leads to a quicker return of cognitive functions and speedier discharge from the Post Anesthesia Care Unit (PACU).

Objectives: The purpose of this study is to compare the emergence time and time of return of cognitive functions in patients with general inhalation anesthesia (general anesthesia) maintained to inhalant anesthetics desflurane and sevoflurane, respectively, under standardized conditions.

Material and methods: This study included ASA I and II patients undergoing colorectal abdominal surgery who were randomly assigned into two groups: the first group received the inhalation anesthetic desflurane in combination with the analgesic remifentanil for anesthesia maintenance, while the second group was kept under using sevoflurane in combination with fentanyl. We used standard hemodynamic monitoring, the Train of Four (TOF) and the Bispectral Index System (BIS) to determine the depth of an anesthesia. We recorded the time required for extubating, the opening of the eyes, verbal response, the modified Aldrete score of 9, the Mini Mental State Examination (ММSE) of 25 and the Short Orientation-Memory-Concentration Test (OMCT).

Results: The results, expressed in minutes and obtained in both patient groups, demonstrate a significantly shorter time for regaining cognitive functions in the patients who received a desflurane inhalation anesthetic with remifentanil compared to the patients who received a sevoflurane inhalation anesthetic with fentanyl. This is thought to be due to the faster pharmacokinetic profile of desflurane, leading to an accelerated elimination in the patients. Desflurane, in combination with remifentanil, a short-acting opioid, further shortens the recovery time of cognitive functions.

Conclusion: This study underscores that the time required for early recovery from anesthesia is markedly shorter in patients receiving desflurane compared to patients given sevoflurane when administering general anesthesia. This finding emphasizes the potential benefits of desflurane in optimizing perioperative outcomes, including faster emergence from anesthesia and cognitive recovery.

Key Words: cognitive function, desflurane, inhalational anesthetics, opioid,  sevoflurane.

 

Introduction

 

As developed countries push to save hospital resources, doctors are under increasing pressure to develop targeted strategies for a faster postoperative recovery of patients and, thus, a shorter hospital stay. Desflurane and sevoflurane are inhalant anesthetics with clinical and pharmacological profiles that make them ideal for the rapid recovery of patients (1,2). The development of minimally invasive surgical techniques has led to an increased need for rapid awakening of patients from general anesthesia after surgical procedures. An anesthesiologist can make a difference through physiological mechanisms that relieve pain and shorten the time it takes to recover protective reflexes, especially those related to the airways, and regain cognitive functions. As a result, there is an increasing need for anesthetics that induce sufficiently deep anesthesia while making the emergence from it quick, i.e. quickly restoring vital functions without any side effects (3).

Inhalation anesthetic agents are used to induce and maintain general anesthesia, and they are delivered in the patient through a mixture of carrying gases, most commonly air/ oxygen. They exert their effect on the CNS to cause loss of consciousness, the establishment of anesthetic sleep and the loss of the response to harmful stimuli, while the depth of anesthesia is proportional to the partial pressure of an anesthetic in the lungs and brain. Since the concentration of the inhalation aesthetic in these two organs cannot be measured (except in a computer simulation), the alveolar end-tidal partial pressure of the inhalation anesthetic is used as a replacement for the concentration of the inhalation anesthetic at the site of action (4).

Desflurane is a volatile anesthetic that is the latest to enter anesthetic practice and it is used to maintain general anesthesia. It is desirable for surgical techniques that require rapid induction and rapid awakening from anesthesia, such as major and long head and neck surgeries. Its low solubility (blood/gas coefficient of 0.42) and low distribution volume are useful for patients undergoing long surgery and bariatric surgery, in which the distribution volume of drugs soluble in lipids is higher. Desflurane’s pharmacological profile makes it even more suitable for general anesthesia (5). Compared to other inhalation anesthetics, its low solubility makes it easier to reach an equilibrium between alveolar and inspired concentration. Therefore, we have a rapid induction of general anesthesia and rapid awakening from anesthesia. Only a small percentage of desflurane, 0.02%, is metabolized in the body, while 99.98% of it is exhaled unchanged through the lungs.

Cognitive status disorders in the postoperative period are common after major surgeries, and general anesthesia is considered the main cause. Postoperative cognitive disorders can be classified into postoperative delirium, postoperative cognitive dysfunction and dementia (6,7). Postoperative cognitive dysfunction is a mild neurological disorder characterized by impairments in memory, concentration, linguistic understanding and social relationships. The diagnosis is formulated days after surgery and can result in a lifelong decrease to the patient’s quality of life. The pathophysiological mechanism responsible for postoperative cognitive disorders in patients remains unclear (8). Predisposing factors include age and degree of education, presence of a preoperative cognitive disorder, chronic use of opioids and benzodiazepines, the existence of comorbidities, cerebrovascular disorders and the appearance of postoperative delirium (9,10). Other factors that increase the risk of cognitive disorders are duration of anesthesia, re-operation, infection and postoperative pulmonary complications.

Goal

 

The purpose of this scientific study is to examine the effects of volatile anesthetics on patients’ cognitive functions. Therefore, we compare the impact of two inhalation anesthetics, desflurane and sevoflurane act, on the cognitive functions of patients who, due to the type of surgical intervention, had to be placed under general anesthesia. Our second goal is to prove that the short-acting inhalation anesthetic, desflurane, along with the short-acting opioid anesthetic, remifentanil (not fentanyl), is among the best combinations for patients who need a long surgical intervention and general anesthesia with no postoperative impact on cognitive functions. To achieve these two goals, we will evaluate and compare the time of the return of reflexes to the airways and regaining of cognitive functions after general anesthesia with desflurane and sevoflurane, with the former being combined with remifentanil and the latter in a typical combination with fentanyl. All other factors affecting waking time from general anesthesia will be the same for both groups of examinees.

Material and methods

In this observational study conducted at the Clinic for Anesthesia, Resuscitation and Intensive Treatment (KARIL), the University Clinic for Traumatology, Orthopedic Diseases, Anesthesia, Reanimation, Intensive Care and Emergency Centre (UC TOARILUK) over a period of 24 months, included 60 respondents, 26 of whom received halogenated inhalational desflurane (MAC=0.7-1), while 34 respondents received halogenated inhalational sevoflurane (MAC=0.7-1) to administer general anesthesia. In the desflurane group, thirteen subjects received fentanyl intraoperatively, while 13 subjects were maintained under anesthesia by remifentanil, and in the sevoflurane group, 17 received fentanyl, while 17 were maintained under anesthesia by remifentanil. Inclusion criteria for the study encompassed ASA 1.2 and 3 with BMI below 35 and an age limit of 18–65 years for both genders. The subjects received elective general anesthesia with an inhaled anesthetic desflurane or sevoflurane for colorectal pathology during an elective surgery lasting between 2 and 3 hours. The depth of anesthesia was monitored by the Bispectral Monitoring Index, which ranged from 45 to 55 in both groups, corresponding to stage 3 surgical anesthesia. The awakening time from anesthesia was measured from the cessation of the inhalation of an anesthetic to the return of reflexes to the airways (laryngeal reflex). Then, the extubating time was measured, followed by the time of the first opening of the eyes in response to a verbal command, the moment of holding the head raised for 5 seconds, and the orientation to person, place and time, using a modified Aldrete score that needed to be above 9. Cognitive functions were evaluated according to the time required to complete the Mini Mental State Examination (MMSE) test and the Orientation-Memory-Concentration Test (OMCT), which were filled in for each patient 4 times: preoperatively, in the recovery room (PACU) and on the first and second postoperative days. The study’s exclusion criteria were ASA over 3, age under 18 and over 65 years, morbid obesity, BMI over 35, existence of neuromuscular diseases, history of possible malignant hyperthermia, obstructive lung disease with regular use of bronchodilators and the presence of preoperative cognitive disorder, which originates from chronic opioid or benzodiazepine use, as well as cerebrovascular disorders.

 

Work protocol

 

At the operating room, patients were connected to a monitor to observe the ECG, non-invasive blood pressure, pulse oximetry and Bispectral Index. A peripheral neurostimulator was installed to monitor The Train of Four (TOF). The patients were reoxygenated with 100% oxygen within 3 minutes with a flow of fresh gases of 6L/min and anesthesia was induced with a standardized induction approach using sedative midazolam 0.03mg/kg i.v., fentanyl 1-2mcg/kg, propofol 2mg/kg and muscle relaxant rocuronium 0.6mg/kg. The respiratory pathway was secured with an adequately-sized endotracheal tube and connected to an anesthesiology ventilation machine with an inhaled anesthetic desflurane (3–6%), (1–2%) to mas=0.7–1, with a flow of fresh gases of 2L/min, 50% air with 50% oxygen. Tidal capnography etSO2, the inspiratory faction (Fi) of anesthetic gases and the expiratory faction (FE) of volatile anesthetics were monitored. Minute ventilation was set with a respiratory volume of 6–8ml/kg, a 12/min respiratory frequency and an inhale exhale ratio of 1:2 to maintain a 30–40mmHg CO2 tidal. The dosage for maintenance of intravenous and inhaled anesthetic agentswas titrated to maintain BIS from 45–55. Additional bolus doses of fentanyl at a dose of 0.5mcg/kg were given as needed. Remifentanil was given at a dose of 0.125–0.25mcg/kg/min. Muscle relaxation was maintained with intermittent doses of rocuronium at a dose of 0.15mg/kg. The volatile anesthetic was reduced 15 minutes before the surgery ended to MAS=0.5 and was interrupted after the last surgical stitch was placed. The flow of fresh gases was then increased to 6L/min with 100% oxygen. After achieving TOF≥3, a reversion of the neuromuscular block with Neostigmine 0.03mg/kg and Atropine 0.01mg/kg was administered. i.v..

 

Statistical analysis

The data analysis was performed in statistics programs Statistics 7.1 for Windows and SPSS 23, in series of numerical variables (ASA, age, BMI, length of intervention), Description Statistics (Mean; Std. Deviation; ±95,00%CI; Median; Minimum; Maximum). The difference between the values of the parameters analyzed in relation to the gender of the respondents was done by applying t-test, independent, by groups (t/p) depending on the distribution of the data. The correlation between two variables was derived with Pearson’s correlation coefficient (r) and Spearman Rank Order R (R), depending on the distribution of the data. Significance was determined for p<0.05.

Results

The results (expressed in minutes) obtained in the both patient study groups are significantly shorter in the group of patients who received a desflurane inhalation anesthetic with the opioid remifentanil, compared to the group of patients who received a sevoflurane inhalation anesthetic with fentanyl or remifentanil, when administering elective general anesthesia.

Table1. Demography and duration of surgical intervention.

 

Group D-f.

(n=13)

 Group D-r.

(n=13)

 Group S-f.

(n=17)

 Group S-r.

(n=17)

 p-value
Sex (m/f) 8/5 7/6 9/8 10/7 p<0.05*
ASA I/II/III 2/6/5 1/6/6 2/9/6 1/8/7 p<0.05*
Age 61±8.7 63±7 64±9.3 62±8.1 p<0.05*
BMI 22.23±.1 21±7 PM 23.5±4.0 22.2±3.1 p<0.05*
Length of intervention 149.4±11.2 151.1±9.3 157±8.5 156±7.7 p<0.05*

         BMI=Body Mass Index, ASA=Physical Status Classification System, Group D-f=Fentanyl Desflurane, Group D-r=Remifentanil Desflurane, Group S-f=Fentanyl Sevoflurane, Group S-r=Sevoflurane with Remifentanil

 

  • The group maintained under anesthesia by desflurane with remifentanil, marks a shorter time of extubating, from the last surgical stitch of the operational operation, i.e., from discontinuation of the inhalation anesthetic to extubating.
  • The patients with desflurane-remifentanil anesthesia mark shorter time of the opening of the eyes, the time from the last surgical stitch, from the cessation of the inhalation of anesthetic to the opening of the eyes in response to a verbal command given by the examiner.
  • Patients with desflurane-remifentanil mark shorter time of a verbal response after the last surgical stitch.
  • The desflurane-remifentanil group marks shorter time from discontinuation of the inhalation anesthetic to achieving Aldrete’s score of 9.
  • Cognitive function returns more quickly to the desflurane group after the patient’s awakening, i.e. the time from interruption of desflurane to time required to complete the Mini Mental State Examination (MMSE) in the recovery room with a score of more than 25 is shorter in the desflurane-remifentanil group.
  • The Mini Mental State Examination (MMSE) test on the first postoperative day showed a higher score of cognitive function by patients who received desflurane-remifentanil.
  • Patients who received desflurane-remifentanil achieved a better score on the Orientation-Memory-Concentration Test (OMST) when they were examined for the second time, i.e. in the recovery room.

Table 2. Time of emergence from anesthesia.

Group D-f Group D-r Group C-f Group S-r        r value
Extubating 7.2 ±1.6 7±8.3 8.9 ±2.0 8.4±1.1 p<0.05*
Eye opening 6.8 ±3.1 6.5±5.4 7.5 ±4.2 7.1± 3.4 p<0.05*
Verbal response 7.6 ±1.8 7.2±2.0 9.3 ±4.1 8.2±2.6 p<0.05*
Modified Aldrete score>9 13.3 ±5.0 13.1±1.2 16.7 ±3.9 15.5±4.4 p<0.05*
MMSE>25 60 ±7.2 57.8±1.8 64.3 ±3.3 61.3±3.4 p<0.05*
OMST<10 74±2 72±3.7 77.71±2.3 74.3±6.3 p<0.05*

MMSE=Mini Mental State Examination Test, Orientation-Memory-Concentration Test (OMCT) Group D-f=Fentanyl Desflurane, Group D-r=Remifentanil Desflurane, Group S-f=Fentanyl Sevoflurane, Group S-r=Remifentanil Sevoflurane

 

Discussion

The purpose of this study was to compare the waking time and time of return of cognitive functions in patients after elective general anesthesia maintained with inhalant desflurane in one group of patients, and inhalant sevoflurane in another group of patients. The inhaled anesthetics were combined with opioid anesthetics, fentanyl or remifentanil.

The results showed that the waking time in all patients maintained under anesthesia by a desflurane was shorter than that of patients maintained under anesthesia by sevoflurane. The extubating time with desflurane anesthesia was 7.2 ±1.6 minutes, which was significantly shorter than the time of extubation with sevoflurane, 8.9 ±2.0 minutes, while the verbal response time for desflurane anesthesia was significantly smaller, 7.6 ±1.8 minutes, versus the time of verbal response to sevoflurane anesthesia, which was 9.3 ±4.1 minutes. This is thought to be due to the faster kinetic profile of desflurane, which leads to a faster elimination from the patient. We used the Bispectrality Monitoring Index, BIS, to ensure an adequate depth of anesthesia, i.e. to achieve values between 40 – 60, correlated with loss of consciousness and surgical anesthesia, and independence between the two inhalation agents. The BIS value was compared at the introduction to anesthesia and during waking up.

After the cessation of the inhalation anesthetic and after the last stitch was made, in the early postoperative period, higher BIS values were observed in the desflurane group with opioid remifentanil, unlike the sevoflurane fentanyl group, where BIS values increased later.

 

Conclusion

 

The resulting values obtained from the cognitive function tests in the recovery room showed that in patients maintained under anesthesia by desflurane and remifentanil, cognitive functions returned faster than in patients maintained under anesthesia by desflurane-fentanyl. The same results were obtained in the sevoflurane-remifentanil group compared to the sevoflurane-fentanyl group.

This study contributed to an awareness of the differences in impact between the two inhalation anesthetics on cognition and remembering after waking up from general anesthesia. However, like any research, it can be extended through further studies with their own findings, eighter they are positive or negative, from which we distance ourselves. This study did not measure the level of inhalation anesthetics in the operating room, as gases are eliminated through an evacuation system in the external environment, nor has the concentration of the inhalation anesthetic been measured in the external environment. Desflurane is known to damage the ozone hole, but it cannot affect as much as global warming affects the country’s weather disasters. We leave this field of research to the specialists that deal with it.

 

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