Effects of remifentanil dose on surgical conditions during endoscopic sinus surgery

doi:10.21203/rs.3.rs-2833834/v1

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Effects of remifentanil dose on surgical conditions during endoscopic sinus surgery

https://doi.org/10.21203/rs.3.rs-2833834/v1

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published 29 Aug, 2023

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Background The combination of propofol and remifentanil results in better surgical field conditions during endoscopic sinus surgery than inhalation anaesthesia. This study compared surgical field conditions between groups receiving low or high concentration of remifentanil.

Methods Fifty-four patients, ASA I or II were used to assign the patients to either the high-concentration remifentanil group (HR), targeted at 8 ng/mL or the low-concentration remifentanil group (LR), target was 4 ng/mL Surgical condition was evaluated using the Boezaart Surgical Field Grading Scale presented by Boezaart.

Discussion When comparing the HR group and the LR group, the surgeon observed a significant difference in surgical conditions. The reason was the significant decrease in cardiac output. This reduction was because of the effect of remifentanil on reducing heart rate rather than stroke volume.

Trial Registration Clinical Trial Registry of the Republic of Korea (KCT0006453)

Endoscopic sinus surgery

Remifentanil

Surgical field condition

Endoscopic sinus surgery is an important treatment method for sinusitis and is most often performed under general anaesthesia[1]. One of the major drawbacks of performing surgery under general anaesthesia is increased bleeding, which can cause difficulty in manipulating the endoscope due to decreased visibility[2].

Many studies have been conducted to reduce bleeding during surgery, and total intravenous anaesthesia (TIVA) using the combination of intravenous anaesthetic propofol and the opioid remifentanil can reduce bleeding and improve surgical conditions (SC) compared to inhalational anaesthesia[3].

The primary objective of this study was to compare high-concentration (8 ng/ml) remifentanil use to low-concentration (4 ng/ml) remifentanil use on the conditions of surgery. The secondary objective was to compare hemodynamic variables of cardiac output, stroke volume, heart rate, and mean arterial pressure between the two groups.

- Study subjects

The subjects were 54 patients between the ages of 18 and 65 years who were rated as American Society of Anesthesiology Classification I or II. Exclusion criteria were: 1) patients with allergies to eggs or soybean oil; 2) patients with a history of drug abuse; and 3) patients receiving other medical treatment, e.g., for hypertension, diabetes, or other conditions. After obtaining approval from the hospital’s institutional review board (Hanyang University Guri Hospital Institutional Review Board, GURI 2012-03-041-006) and registering with the clinical research information service centre ( KCT0006453, Date of registration:17/08/2021, Principal Investigator: SY Cho), this study was performed in accordance with the relevant guidelines and regulations. This study was in accordance with the declaration of Helsinki. Written informed consent was obtained from the patients who voluntarily agreed to participate in the study. The subjects were randomly classified into a high-concentration remifentanil group (HR) and a low-concentration remifentanil group (LR) using computer-generated numbers.

- Research methods

After the patient arrived at the operating room, electrocardiogram, pulse oxygen saturation, non-invasive blood pressure, and end-tidal carbon dioxide pressure were measured. Depth of anaesthesia was measured using a bispectral index (BIS) monitor (A-2000TM, version 3.3, Aspect Medical Systems Inc., Newton, MA, USA). After administering 100% oxygen for three min to the patient, 40 mg of 1% lidocaine was administered intravenously. Using a target concentration-controlled injector (Orchestra, Fresenius-Vial, Brezins, France), propofol was administered at an effect-site concentration of 6.0 µg/ml using a Schnider pharmacokinetic model. Remifentanil was administered at an effect-site concentration of 2.0–4.0 ng/ml using the Minto pharmacokinetic model. During administration of propofol and remifentanil, the patient received the instruction "open your eyes" every 10 seconds. If the patient could not open their eyes, the muscle relaxant esmeron was injected at a dose of 0.6 mg/kg. When the BIS level dropped below 60 and the train of four (TOF) on the nerve stimulator reached zero, endotracheal intubation was performed.

Administration of remifentanil during anesthesia maintenance was performed by a target-controlled infusion (TCI) device with an effective site concentration of 8 ng/ml in the high-concentration group and of 4 ng/ml in the low-concentration group. The TCI device was prepared in advance, and the fixed concentration of drug was sealed. The anesthesiologist who administered the anesthesia was, therefore, blinded to the concentration of remifentanil used. The effect-site concentration of propofol was adjusted by 0.2 µg/ml from the initial concentration to maintain a BIS value of 40–60.

At the end of the operation, propofol and remifentanil were discontinued; pyridostigmine 0.2 mg/kg and glycopyrrolate 0.008 mg/kg were injected intravenously to reverse the muscle relaxant effects; and extubation was performed under the influence of a nerve stimulator.

Baseline systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), heart rate (HR), BIS, stroke volume (SV), and cardiac output (CO) levels were measured immediately after arrival at the operating room. The variables also were measured immediately after endotracheal intubation and at 30, 60, and 90 minutes after the start of surgery, for observation and comparison. Stroke volume and cardiac output were measured using non-invasive cardiac monitoring, for which the CSN-1901 (Nihon Kohden, Tokyo, Japan) was used. Evaluation of the surgical condition was conducted by a single operator using the Boezaart surgical field grading scale (Table 1)[4] and was recorded at 30, 60, and 90 minutes after the start of surgery.

Table 1

Surgical Grading Scoring System Designed Specifically for Use in Endoscopic Sinus Surgery
Grade	Assessment
0	No bleeding (cadaveric conditions)
1	Slight bleeding – no suction required
2	Slight bleeding – occasional suction required
3	Slight bleeding – frequent suctioning requied; bleeding threatens surgical field a few seconds after suction is removed
4	Moderate bleeding – frequent suction ing required and bleeding threatens surgical field directly after suction is removed
5	Severe bleeding – constant suctioning requied; bleeding appears faster than can be removed by suction; surgical field severely threatened and surgery usually not possible

The total doses of propofol and remifentanil administered during anesthesia were recorded.

After 30 minutes and within 24 hours of recovery room arrival, the Visual Analog Scale (VAS) and Postoperative Nausea and Vomiting (PONV) score were measured. The PONV score was divided into 4 categories, 0 = none, 1 = nausea, 2 = retching, and 3 = vomiting.

-Sample size calculation

We used the mean and standard deviation from pilot study (mean and standard deviation: 2.3 and 0.57). In a two-tailed analysis where α = 0.05 and β = 80%, 24.1 patients were required to obtain a 20% difference in the mean between the experimental and control groups. A total of 54 patients were required to maintain acceptable statistical power, assuming a 10% dropout rate.

- Statistics

The Statistical Package for Social Sciences 20.0 for Windows (SPSS Inc., IL, USA) was used as a statistical program. The Mann-Whitney rank sum test was performed to compare numerical data between the two groups, and the χ2 test and Fisher's exact test were used for non-parametric data. Kruskal-Wallis one-way analysis of variance with a Dunn multiple comparison test was used to assess haemodynamic change. The statistical significance level was set at p = 0.05.

All 54 patients who participated in the study met the inclusion criteria, and none refused to participate. These patients were randomly assigned to a high-concentration or low-concentration group, with 27 patients in each group (Fig. 1).

Subject data and clinical characteristics are presented in Table 2. There was no significant difference between the two groups in terms of mean age, gender, height, weight, body mass index, ASA score, and operation and anaesthesia times.

Table 2

Demographic Data and Clinical Characteristics of Patients
	Group LR (n = 27)	Group HR (n = 27)
Age (yr)	44 ± 12.0	47.1 ± 13.0
Gender (M/F)	9/18	9/18
Height (cm)	167.1 ± 8.8	167.6 ± 9.0
Weight (kg)	69.7 ± 13.0	69.1 ± 14.3
Body mass index (kg/m²)	25.0 ± 4.1	24.5 ± 3.4
ASA (I/II)	10/17	11/16
Operation time (min)	108.3 ± 30.0	102.8 ± 22.8
Anaesthesia time (min)	138.3 ± 28.2	135.7 ± 22.0
Values are number or mean ± SD. Group LR: low remifentanil group, Group HR: high remifentanil group, ASA: American Society of Anesthesiologists physical status.

Haemodynamic variables between the two groups were measured through non-invasive cardiac monitoring (Table 3). For cardiac output, there was a statistically significant decrease in the HR compared to the LR group immediately after endotracheal intubation and at 30, 60, and 90 minutes after the start of surgery (cardiac output, base; p = 0.222, intubation; p = 0.016, 30 min; p = 0.014, 60 min; p = 0.012, 90 min; p = 0.008). However, for stroke volume, there was no significant difference between the two groups in all measurements (stroke volume, base; p = 0.482, intubation; p = 0.461, 30 min; p = 0.258, 60 min; p = 0.263, 90 min; p = 0.603).

Table 3

Haemodynamic Parameters
	Group LR (n = 27)	Group HR (n = 27)
Cardiac output, Base	7.20 ± 1.45	6.31 ± 2.34
Cardiac output, Intubation	7.34 ± 1.32	5.87 ± 1.81*
Cardiac output, 30	6.32 ± 1.28	5.00 ± 1.53*
Cardiac output, 60	6.45 ± 1.47	4.98 ± 1.56*
Cardiac output, 90	6.83 ± 1.37	5.18 ± 1.83*
Stroke volume, Base	92.4 ± 14.4	87.8 ± 20.7
Stroke volume, Intubation	88.2 ± 14.5	83.9 ± 17.0
Stroke volume, 30	89.3 ± 16.1	82.5 ± 16.9
Stroke volume, 60	88.5 ± 16.4	81.4 ± 18.1
Stroke volume, 90	88.1 ± 14.9	84.8 ± 19.8
The values are measured by non-invasive cardiac monitoring with CSN-1901. Base: preoperative control values; Intubation: immediately after intubation; 30, 60, and 90: 30 min, 60 min, and 90 min, respectively, after beginning the operation. *p < 0.05 compared to Group LR.

The changes in heart rate between the two groups [Fig. 2. (a)] were significantly lower in the high-concentration group compared to the low-concentration group immediately after endotracheal intubation and at 30, 60, and 90 minutes after the start of surgery (heart rate changes, base; P = 0.412, intubation; p = 0.033, 30 min; p = 0.005, 60 min; p = 0.002, 90 min; p = 0.001). Mean arterial pressure [Fig. 2(b)] and systolic blood pressure [Fig. 2 (c)] decreased in the high-concentration group compared to the low-concentration group immediately after endotracheal intubation and at 30 minutes after the start of surgery; however, these differences were not statistically significant. At 60 and 90 minutes after the start of surgery, the high-concentration group showed statistically lower MAP and SBP than the high-concentration group (mean arterial pressure, base; p = 0.692, intubation; p = 0.765, 30 min; p = 0.121, 60 min; p = 0.006, 90 min; p = 0.025, systolic arterial pressure, base; p = 0.786, intubation; p = 0.144, 30 min; p = 0.081, 60 min; p = 0.039, 90 min; p = 0.019).

Surgical conditions (Table 4) did not show significant differences between the two groups at 30 and 60 minutes after the start of surgery. However, at 90 minutes after the start of surgery, the high-concentration group showed a significantly lower score than the low-concentration group (surgical score, 30 min; p = 0.315, 60 min; p = 0.269, 90 min; p = 0.021). There was no significant difference between the two groups in terms of postoperative pain, nausea, and vomiting (VAS score, p = 0.991, PONV score, p = 0.077).

Table 4

Changes of Surgical Scores and Other Parameters During Endoscopic Sinus Surgery
	Group LR (n = 27)	Group HR (n = 27)
Surgical score, 30	2.33 ± 0.62	2.56 ± 0.63
Surgical score, 60	2.67 ± 0.62	2.44 ± 0.51
Surgical score, 90	2.80 ± 0.68	2.25 ± 0.58*
Total propofol dose (mg)	1127.4 ± 374.5	984.2 ± 304.1
Total remifentanil dose (mcg)	1221.2 ± 347.3	2192 ± 719.2*
VAS	4.19 ± 2.24	4.19 ± 2.35
PONV	0.11 ± 0.32	0.00 ± 0.00
VAS: visual analogue score, PONV: postoperative nausea and vomiting. *p < 0.05 compared to Group LR.

This study demonstrated a significant decrease in surgical score in the high-concentration group after 90 minutes of surgery compared to the low-concentration group. Cardiac output was also significantly decreased.

Endoscopic sinus surgery is an important treatment for chronic sinusitis and identification of anatomical landmarks within the limited surgical field of view is important for successful surgery[3]. Under general anaesthesia, increased bleeding may obscure endoscopic surgical visibility and hinder surgery. This can lead to complications such as increased postoperative haemorrhage, cerebrospinal fluid leakage, and visual loss[5]. To reduce these risks, use of the reverse Trendelenburg position, topical decongestants, and vasoconstrictors has been suggested[6]. In addition, controlled hypotension using general anaesthesia has been used to reduce bleeding during endoscopic sinus surgery[7]. Use of drugs such as vasodilators, sodium nitroprusside, or beta-blockers has also been suggested to reduce blood pressure[8–10]. Total intravenous combination anaesthesia using intravenous anaesthetic propofol and the opioid remifentanil is also widely used to reduce intraoperative bleeding by reducing cardiac output without rapidly decreasing systemic vascular resistance.³

Remifentanil, an ultrashort-acting synthetic opioid, may show a synergistic effect with propofol during total intravenous anaesthesia, causing a decrease in cardiac output. This is probably due to the bradycardia-inducing effect along with a blood pressure-lowering effect[11]. In this study, we confirmed that heart rate decreased significantly in the high-concentration group compared to the low-concentration group. Several reports have suggested that the bradycardic effect of remifentanil is associated with its central vagotonic effect[12]. A significant decrease in cardiac output was also observed in the high-dose group. However, stroke volume did not show a significant difference between the two groups. Based on these results, the decrease of cardiac output in the high-concentration group appears to be more strongly related to decrease in heart rate than to decrease in stroke volume. Cheong et al[13]. reported neither a decrease in myocardial contractility proportional to the increase in remifentanil usage nor a compensatory increase in myocardial contractility with a decrease in heart rate.

Manola et al.[14] reported that the blood pressure-lowering effect of remifentanil was due to the reduction of cardiac output rather than peripheral vasodilation. In this study, there was a significant MAP difference between the two groups at 60 min and 90 min after start of the surgery. Surgical conditions, a measure of the quality of the endoscopic view, showed a significant difference between the two groups at 90 minutes after the start of surgery. Based on these results, we confirmed that use of high-concentration remifentanil can cause a decrease in cardiac output and can assist the surgeon in maintaining the necessary view during endoscopic surgery.

In this study, cardiac output and stroke volume were measured through non-invasive cardiac monitoring (CSN-1901). CSN-1901 monitoring is based on pulse wave transit time and indirectly measures cardiac output and stroke volume through the R-wave of the electrocardiogram, the pulse waves of the pulse oximeter, and blood pressure. Traditionally, cardiac output has been measured through an invasive method such as a pulmonary artery catheter; the use of this measurement method is gradually decreasing, while the use of non-invasive measurement methods is increasing[15, 16]. Saugel et al.[15] compared the types and mechanisms of non-invasive cardiac monitoring with invasive measurement methods, and Jeon et al.[17] reported that use of the CSN-1901 is helpful to estimate intravascular volume status.

A limitation of this study may be the surgical grading system that evaluated the surgical field of view. In this study, the surgical condition was evaluated through the Boezaart grading scale. This evaluation method is widely used because of its simplicity but is somewhat subjective and remains unstandardized. Athanasiadis et al.[2] reported that most reported scores on the Boezaart grading scale were 2 or 3 points, hindering detection of subtle differences in the surgical field. Also, inter-rater reliability was lower than with the Wormald surgical field grading scale. In addition, since scoring is performed using a subjective numerical scale, reviewer bias may occur; and the score at 30 minutes after the start of surgery may affect the scores at 60 and 90 minutes after the start of surgery.

A further study is needed to compare the measured values using different methods of cardiac output monitoring. In this study, cardiac monitoring was based on pulse wave transit time. If we can compare the results of this study with cardiac output measurement through echocardiography, in-depth testing of the reliability and accuracy of non-invasive monitoring will be possible.

In conclusion, when comparing the HR group with the LR group, there was a marked difference in surgical conditions as graded by the surgeon. The reason for this is that cardiac output significantly decreased when a high concentration of remifentanil was used because of remifentanil’s effect on reducing heart rate rather than stroke volume.

Declaration of interests: The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

This study was approved by the the hospital’s institutional review board (Hanyang University Guri Hospital Institutional Review Board, GURI 2012-03-041-006) and registered with the clinical research information service centre (KCT0006453, Date of registration:17/08/2021, Principal Investigator: SY Cho). This study was in accordance with the declaration of Helsinki and performed in accordance with the relevant guidelines and regulations. All patients voluntarily participated in the study and signed informed consent before the surgery.

Consent for publication

Not applicable

Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request

Competing interests

The authors declare that they have no competing interests

Funding

Not applicable

Author’s contributions

JHJ, CWP, YJY, DJL, SYC: revised this manuscript.

All authors have read and approved final manuscript

Acknowledgements

The authors thank the Hanyang University E-world center for considerable help during the preparation of the manuscript.

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Brunner JP, Levy JM, Ada ML, Tipirneni KE, Barham HP, Oakley GM, et al. Total intravenous anesthesia improves intraoperative visualization during surgery for high‐grade chronic rhinosinusitis: a double‐blind randomized controlled trial. Int Forum Allergy Rhinol. 2018, 1114-22.
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No competing interests reported.

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Journal Publication

published 29 Aug, 2023

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Effects of remifentanil dose on surgical conditions during endoscopic sinus surgery

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