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February-B 2021, Volume 71, Issue 2

Original Article

Comparison of blood pressure and pain rating index used for depth regulation of sevoflurane anaesthesia

Jianwen Zhang  ( Department of Anesthesiology, Shanxi Dayi Hospital, Taiyuan, China )
Zhigan Lv  ( Department of Anesthesiology, Shanxi Dayi Hospital, Taiyuan, China )
Liping Bai  ( Department of Anesthesiology, Shanxi Dayi Hospital, Taiyuan, China )
Baoguo Wang  ( Department of Anesthesiology, Beijing Sanbo Brian Hospital, Capital Medical University, Beijing, China. )

Abstract

Objective: The Pain Rating index (PRi) is a new parameter for regulating analgesic depth of anaesthesia based on wavelet analysis. The aim of this study was to investigate the feasibility of PRi for depth regulation of sevoflurane anaesthesia.

Methods: We conducted a monocentric randomized controlled study from September 2017 to June 2018 in patients undergoing anterior cervical discectomy and fusion (ACDF) (n=44). Patients were randomly allocated into two groups and assigned 22 cases to each group: systolic blood pressure group (SBP group) and pain rating index group (PRi group). In SBP group, sevoflurane inhalation concentration (Cs) was adjusted to maintain SBP values at baseline values -20%~+20%; in PRi group, Cs was adjusted to maintain PRi values between 50 and 70. The primary endpoint was anaesthesia recovery time. Secondary endpoints included extubation time, sevoflurane consumption, number of intraoperative haemodynamic instability events /interventions, number of adverse events and postoperative visual analogue scale for pain.

Results: Patient demographic characteristics, surgical time and anaesthesia time did not differ between groups. Anaesthesia recovery time was shorter in PRi group than in SBP group (17.5±3.8min vs 21.5±2.8 min; P=0.001). Extubation time was also shorter in PRi group than in SBP group (21.9±1.7min vs 24.1±2.5min; P=0.001). Sevoflurane consumption was lower in PRi group than in SBP group (15.5±4.1ml vs 20.0±2.5ml; P=0.001).

Conclusions: PRi was feasible to regulate depth of sevoflurane anaesthesia, which could shorten anaesthesia recovery time and extubation time, reduce sevoflurane consumption during general anaesthesia in patients undergoing cervical vertebra surgery.

Keywords: Pain rating index; sevoflurane; depth of anaesthesia. (JPMA 71: 590; 2021)

DOI: https://doi.org/10.47391/JPMA.1155

 

Introduction

 

General anaesthesia mainly includes three components: sedation, analgesia and muscle relaxation, only when all three components reach appropriate state at the same time, the ideal depth of anaesthesia could be obtained.1 Currently, there are standard monitoring ways in anaesthesia sedation depth and muscle relaxation depth, but the monitoring of analgesia depth is still in exploration stage.2

The Pain Rating index(PRi) is a new parameter for monitoring analgesic depth of anaesthesia based on wavelet analysis during general anaesthesia. The PRi mainly extracts electroencephalograph (EEG) metadata of repeatable and regular changes in high and low frequency rhythm associated with pain signal and specifically reflect tolerance degree to pain stimulation in the cerebral cortex and subcortical center.3 The range of PRi values is 0-100: 50-70 indicates satisfactory analgesia, <50 suggests excessive analgesia and >70 implies inadequate analgesia. The studies4 showed that the PRi could predict haemodynamic reactivity after tracheal intubation and skin incision in paediatric patients during general anaesthesia.

The previous regulation of sevoflurane anaesthesia depth is mainly based on the monitoring of anaesthesia sedation depth (e.g. bispectral index), but sevoflurane has dose-dependent sedative, analgesic, muscle relaxant and autonomic reflex inhibitory actions. The current clinical trial aimed to investigate the feasibility of PRi for depth regulation of sevoflurane anaesthesia. We hypothesized that PRi was feasible to regulate depth of sevoflurane anaesthesia, which could shorten anaesthesia recovery time and extubation time, reduce sevoflurane consumption in patients undergoing anterior cervical discectomy and fusion.

 

Methods

 

This randomized controlled trial was conducted from September 2017 to June 2018. The trial was approved by Ethical Committee (YXLL-2017-005) and registered in the Chinese Clinical Trial Registry (registration number: ChiCTR-IPR-17012092; date of registration: July 23, 2017). Written informed consent was obtained from all patients. Consecutive patients (age 40-60 years) undergoing elective anterior cervical discectomy and fusion(ACDF) surgery, with body mass index (BMI) 18-25 kg/m2 and American Society of Anaesthesiologists (ASA) physical status classification of I or II were included in the study.

The exclusion criteria were: (1) patients with history of central nervous system or respiratory system disease; (2) patients with abuse of alcohol or illicit drugs; (3) patients with history of malignant hyperthermia; (4) patients with psychiatric history or refused to sign informed consent.

A random number generator assigned the eligible patients into two groups: systolic blood pressure group (SBP group) and pain rating index group (PRi group). The main anaesthesiologist was aware of patient grouping and intervention used. However, all patients and all staff who performed data collection and analysis were blinded to patient grouping and intervention used.

Non-invasive blood pressure (NIBP), pulse oxygen saturation (SpO2), heart rate (HR) and electrocardiogram (ECG) were routinely monitored during surgery in all patients (IntelliVue MX700 bedside patient monitor; Philips, Amsterdam, The Netherlands). For the monitoring of PRi, skin of the patient's forehead and mastoid was degreased with alcohol and  EEG electrodes of  multifunction combination monitor HXD-I (Beijing Easymonitor Technology, Co., Ltd., Beijing, China) were placed  on Patients' forehead, 2cm above midpoint between eyebrows and above bilateral eyebrows, the reference electrodes were placed on bilateral mastoid. The electrode impedance was kept below 7.5kw as required by the manufacturer to ensure optimal contact.

The baseline values for SBP, HR and PRi were defined as average of three consecutive measurements immediately after patients' arrival in operating theater and recorded before anaesthesia induction. During surgery, the anaesthesiologist (who was aware of patient's assignment) managed level of anaesthesia based on the group, patient had been allocated. However, all investigators involved in the collection, recording and analysis of data were blinded to the patient's assignment.

Calculation of PRi was conducted by the following procedure:3,5

For collected EEG signals, under sampling frequency, sampling accuracy and time window, vector set of each waveform signal is generated by discrete processing:

fi (x) = [x1 x2 x3 … xm- 2 xm- 1 xm]

i: number of EEG leads, m: number of vector elements.

Each lead EEG data acquisition window is S seconds, composed of each lead of EEG data vector Ni. Preprocessing of vector data for removal of DC components:

f (x) = f (x) - Av

Av: Direct circuit component of a vector.

For preprocessed brain wave data, wavelet analysis algorithm is applied.  Wavelet algorithm definition:

A set of wavelet transform basis functions for bandpass filter banks can be obtained:

(Wf (2^0, x)), (Wf (2^1, x)), (Wf (2^N, x))

The power WLE of waveform potential of each wavelet base reconstruction function can be obtained

For each guided brainwave vector:

f (x) = [x1, x2, x3... xm-2, xm-1, xm]

The power spectrum function is calculated synchronously, and the formula is calculated by using fast Fourier transform:

The calculation window is n, which can obtain alpha wave component of 8-13hz, the component of delta wave of 0.5-4hz, the theta component of 4-8hz, and the beta wave component of 13-30hz, as well as the dominant frequency, edge frequency and central frequency, and the initial phase pH (hz) of each frequency component.

The generating function was defined as the first derivative of smoothing function, and 64 points were constructed, scaling from 20 to 26 through dyadic wavelet transform.

The weighted items of each sub-index extracted from EEG were acquired through decomposing of different EEG data vectors on transformation characteristic weighting sequence by using multi-layer calculation and multiple regression iteration method. PRi was calculated by combining the weighted items of each sub-index (a1,a2........an as the multiple regression weighting coefficients).

PRi = (a1,a2……an) & (i_22, i_24, i_35, i_52, i_60 ,i_70)

All patients were preoxygenated for five minutes with 100% oxygen. Then intravenous midazolam 0.05mg/kg, sufentanil 0.5ug/kg and etomidate 0.3mg/kg were administered for anaesthesia induction, followed by vecuronium 0.1mg/kg for muscle relaxation. The patient's trachea was intubated and lungs were ventilated mechanically with a tidal volume of 8 to 10 mL/kg, with ventilatory rate adjusted to maintain end-tidal carbon dioxide between 30 and 35 mmHg.

For all the patients, sevoflurane (Maruishi Pharmaceutical Co., Ltd., Osaka, Japan) inhalation concentration (Cs) was started initially at 2 vol% with 2L/min of fresh gas flow. During maintenance of anaesthesia, Cs range was limited between 1.5 vol% and 4 vol%, and vecuronium 0.05mg/kg was administered every forty minutes. In SBP group, Cs was adjusted to keep SBP at baseline values -20%~+20% by increasing or decreasing 0.5 vol% stepwisely. In PRi group, Cs was adjusted to keep PRi values at 50-70 by increasing or decreasing 0.5 vol% stepwisely.

The intraoperative haemodynamic instability events were defined identically for both groups. Hypertension was defined as SBP>120% baseline SBP. Hypotension was defined as SBP<80% baseline SBP. Tachycardia was defined as HR>90 beats per minute if baseline HR was below 75 beats per minute, or HR>120% baseline HR if it was >75 beats per minute. Bradycardia was defined as HR<45 beats per minute.6,7

The intraoperative haemodynamic instability events were treated as follows: 0.3mg of nicardipine was administered intravenously for hypertension, 10mg of esmolol for tachycardia, 10mg of ephedrine for hypotension, and 0.5mg of atropine for bradycardia.6,7

At the end of surgery, sevoflurane was discontinued, and all patients received sufentanil 0.15µg/kg and tropisetron 5mg. Extubation was performed when the patient had recovered respiration and consciousness. Anaesthesia recovery time and extubation time were measured by the investigators blinded to the patient's assignment. All patients were transferred to postanaesthesia care unit (PACU) after extubation. In PACU, the same investigators who were blinded to the patient's assignment assessed postoperative adverse events and pain score.

Anaesthesia recovery time was defined as the time from discontinuation of anaesthetics to spontaneous opening of eyes. Extubation time was defined as the time from discontinuation of anaesthetics to extubation.

The primary endpoint was to evaluate anaesthesia recovery time in this study. The secondary endpoints included (1) sevoflurane consumption; (2) extubation time; (3) the number of intraoperative haemodynamic instability events (hypertension, hypotension, tachycardia and bradycardia); (4) the number of intraoperative interventions (hypertension, hypotension, tachycardia and bradycardia); (5) the number of intraoperative and postoperative adverse events (nausea, vomiting, agitation, respiratory depression and awareness); (6) postoperative visual analogue scale (VAS) for pain.

The primary endpoint of this study was to evaluate anaesthesia recovery time. The sample size calculation was based on the results of a pilot study with 6 cases in each group. In the pilot study, anaesthesia recovery time (mean±standard deviation) was 22.3±2.6min in SBP group and 18.4±3.0min in PRi group, respectively. Therefore, the effect size of 2-groups was 0.91. On the assumption that the allocation ratio of 2-groups was 1, a sample size for each group was 18, calculated by Student's t-test, a level of significance of 0.05, and a power of 0.92. Considering a 20% dropout rate, the sample size for final enrollment was 22 in each group (total 44 patients).

Normally distributed quantitative data are presented as mean ± standard deviation (SD) and were analyzed with Student's t-test. Non-normally distributed data are expressed as median (range) and were analyzed using Brown-Forsythe test. Categorical variables are expressed as n (%) and were analyzed with chi-squared test. A p-value <0.05 was considered statistically significant in all analyses. Statistical analyses were performed using SAS 9.4 statistical software (SAS Institute, Cary, NC, USA). The above data analysis was conducted and completed by two data analysts independently.

 

Results

 

Among 56 patients assessed for eligibility, 5 patients refused to participate, and 7 patients did not meet the inclusion criteria (age<40 years, n=4 and BMI>25 kg/m2, n=3). Therefore, 44 patients were initially enrolled in this study (SBP group, n=22 and PRi group, n=22; Figure-1).

There were no differences in patients'demographic data, surgical time and anaesthesia time between two groups (Table-1).

Anaesthesia recovery time was shorter in PRi group than in SBP group (17.5±3.8min vs 21.5±2.8min; P=0.001). Extubation time was also significantly shorter in PRi group than in SBP group (21.9±1.7min vs 24.1±2.5min; P=0.001). Sevoflurane consumption was also lower in PRi group than in SBP group (15.5±4.1ml vs 20.0±2.5ml; P=0.001) (Table-2).

The total incidence of intraoperative haemodynamic instability events and the incidences of each type of haemodynamic instability events (hypertension, hypotension, tachycardia and bradycardia) did not differ significantly between two groups (P>0.05,Table-3).

The rates of intervention with nicardipine, ephedrine, esmolol and atropine were also similar between two groups (P>0.05,Table-3).

There were no significant differences between groups in the incidences of postoperative nausea/vomiting or agitation (P>0.05, Table-4).

Moreover, postoperative VAS for pain was also similar between groups (P>0.05, Table-4). No patients reported awareness during general anaesthesia, and none experienced postoperative respiratory depression.

 

Discussion

 

The exploration of minimum effective dose of anaesthetic drug under accurate regulation of anaesthesia depth is a pursuit of modern anaesthesiaologists and would help to optimize use of anaesthetic drug, maintain haemodynamic stability, improve quality of anaesthesia and reduce complications of anaesthesia. Traditional monitoring of anaesthesia depth relies on clinical signs that represent the reactions of the body to noxious stimuli during surgery such as blood pressure or heart rate changes, body movement, sweating, lacrimation, eye movement and pupillary reflex.8 However, these indicators have poor specificity and could be influenced by many factors, including other drugs used in combination with general anaesthetics. Thus, there is considerable interest in the development of better methods for monitoring the depth of anaesthesia.

The main findings of the present randomized controlled trial were that regulation of sevoflurane anaesthesia depth with PRi in patients undergoing cervical vertebra surgery shortened anaesthesia recovery time and extubation time, reduced sevoflurane consumption, as compared with regulation by monitoring of conventional clinical signs(SBP). Furthermore, the use of PRi to regulate anaesthesia depth was not associated with any increases in intraoperative haemodynamic instability events or postoperative adverse events or any negative impacts on postoperative pain scores. Taken together, our data suggested that monitoring of PRi is a feasible method of regulating the depth of anaesthesia and might have advantages over conventional monitoring of clinical signs.

The pain is based on the existence of consciousness. During general anaesthesia, the patients' consciousness disappears, and "pain" is mainly manifested as nociceptive stress response, so regulation of anaesthesia depth is essentially the regulation of balance between nociceptive stimulation and anti-nociceptive effects of anaesthesia, that is, the regulation of analgesia depth. Accurate regulation of analgesia depth during general anaesthesia could help to guide rational use of analgesic drugs and improve quality of anaesthesia. In recent years, the exploration and development of Surgical Stress Index (SSI),6,7,9-12 Tip Perfusion Index (TPI)13 and Analgesia Nociception Index (ANI)14-18 have greatly improved the regulation of analgesia depth. However, the clinical application of these indexes is limited due to various complex factors.  At present, there is still lacking an advanced and reliable objective quantitative measure of pain used to guide clinical practice.

For two decades, depth of anaesthesia monitors have been on the market to predict the hypnotic effect of intravenous as well as volatile anaesthesia.19 The new trend is to include predictions of the nociception/ antinociception balance as well. In recent years, a number of studies have found that pain can cause significant and specific changes in multi-brain region and multi-frequency EEG signals, and EEG could reflect the changes in brain caused by anaesthetics.20,21 The newest study found that, based on acquisition of original EEG signal, using the wavelet transform to analyze EEG data, might be used to reflect degree of chronic pain in humans.22 However, the above studies only remain at the level of theoretical research, and do not yet form a reliable and convenient quantitative indicator for clinical practice.

The PRi (range 0-100) is a new parameter for regulating analgesic depth of anaesthesia based on wavelet analysis technology, which is a multi-scale refined analysis of the original EEG wave achieved using scaling and translation functions.3 The principle of this method is to extract metadata of repeatable and regular changes in high and low frequency rhythms associated with pain signals from EEG, and specifically reflect the degree of tolerance to pain stimuli in the cerebral cortex and subcortical center.3,23,24 In this study, the equipment for PRi analysis was multifunctional monitor HXD-I  developed by Chinese researchers in July 2015, which collects left and right two-channel EEG signals from prefrontal lobe, and reduces the complexity of features through continuous and discrete wavelet transform. The continuous wavelet transforms, binary discrete wavelet transform and frequency domain reconstruction algorithm in wavelet analysis were first introduced to deal with the specific EEG data vector.5 This study found that compared with SBP group, both anaesthesia recovery time and extubation time were significantly shortened, and sevoflurane consumption decreased significantly in PRi group, suggesting that PRi was feasible in regulating depth of sevoflurane anaesthesia, and was better than the clinical experience in its regulation.

We found that PRi had some limitations in this study. First, PRi value was susceptible to electrotome's interference and postural changes. Secondly, PRi value changed greatly and had more transient change, which led to limitation in guiding clinical drug regulation. These limitations all affected its clinical application in regulation of anaesthesia depth, so we should continuously improve monitoring parameters and anti-external interference performances.

This study was an exploratory single-center study, the sample size was small and the type of surgery was simple. In addition, the application of vasoactive drugs (such as nicardipine or ephedrine) might affect the calculation of PRi value.

 

Conclusion

 

In summary, the current study confirmed that PRi was feasible to regulate depth of sevoflurane anaesthesia, which could shorten anaesthesia recovery time and extubation time, reduce sevoflurane consumption during general anaesthesia in patients undergoing cervical vertebra surgery. The study would also provide ideas and clinical data for the management of accurate anaesthesia and enhanced recovery after surgery

 

Disclaimer: I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part.

Cconflict of Interest: The authors declare that they have no conflicts of interest.

Funding Sources: Key Research and Development (R&D) Projects of Shanxi Province (201803D31135).

 

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