Accepted Manuscript Intraoperative blood loss during orthognathic surgery: a comparison of remifentanilbased anesthesia with sevoflurane or isoflurane Yumiko Wakasugi, D.D.S, Ph.D, Post graduate Student, Nobuyuki Matsuura, D.D.S, Ph.D, Senior Assistant Professor, Tatsuya Ichinohe, D.D.S, Ph.D, Professor and Chairman PII:
S0278-2391(15)00408-5
DOI:
10.1016/j.joms.2015.03.076
Reference:
YJOMS 56776
To appear in:
Journal of Oral and Maxillofacial Surgery
Received Date: 22 January 2015 Revised Date:
23 March 2015
Accepted Date: 29 March 2015
Please cite this article as: Wakasugi Y, Matsuura N, Ichinohe T, Intraoperative blood loss during orthognathic surgery: a comparison of remifentanil-based anesthesia with sevoflurane or isoflurane, Journal of Oral and Maxillofacial Surgery (2015), doi: 10.1016/j.joms.2015.03.076. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Original article
remifentanil-based anesthesia with sevoflurane or isoflurane
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Title: Intraoperative blood loss during orthognathic surgery: a comparison of
*Post graduate Student
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and Tatsuya Ichinohe, D.D.S, Ph.D‡
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Authors: Yumiko Wakasugi, D.D.S, Ph.D,* Nobuyuki Matsuura, D.D.S, Ph.D,†
†Senior Assistant Professor
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‡Professor and Chairman
Institution: Department of Dental Anesthesiology, Tokyo Dental College, Chiba,
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261-8502, Japan.
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Corresponding author: Yumiko Wakasugi E-mail: [email protected] Address: Department of Dental Anesthesiology, Tokyo Dental College 1-2-2, Masago, Mihama-ku, Chiba-shi, Chiba, 261-8502, Japan. Int. phone: +81-43-270-3970 Int. fax: +81-43-270-3971
ACCEPTED MANUSCRIPT Abstract
Purpose: The aim of this study was to compare blood loss in remifentanil-based
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anesthesia with sevoflurane or isoflurane during orthognathic surgery.
Patients and Methods: In this randomized controlled clinical trial, patients who were
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scheduled for orthognathic surgery were divided into one of two groups; sevoflurane
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group (Sevo group) and isoflurane group (Iso group). Anesthesia was maintained using end-tidal concentrations of 1.4% sevoflurane or 0.9% isoflurane. Remifentanil was continuously infused at 0.05–0.5 µg/kg/min to maintain mean blood pressure
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(MBP) at 60–65 mmHg. Intraoperative blood loss (mL/kg) was compared. Student ttest for unpaired samples was used for statistical analysis. P < 0.05 was considered
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statistically significant.
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Results: The study sample was composed of 19 men and 45 women (n = 64). The mean age was 25 years (range, 16 to 50 years). Intraoperative blood loss tended to be higher in the Iso group (n = 32) (4.79 ± 3.22 mL/kg) compared with the Sevo group (n = 32) (4.00 ± 1.98 mL/kg), while there was no significant difference between the two groups.
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ACCEPTED MANUSCRIPT Conclusion: In a comparison of intraoperative blood loss in remifentanil-based anesthesia with sevoflurane or isoflurane during orthognathic surgery, no difference
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Key words: blood loss; anesthesia; sevoflurane; isoflurane
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was observed between the two groups.
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ACCEPTED MANUSCRIPT Introduction
Oral and maxillofacial surgery (OMS), and particularly orthognathic surgery, is
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performed in areas of high blood flow including the oral mucosa and bone marrow. Blood loss during surgery can obstruct the visual field, prolong operating times, and
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increase the risk of a blood transfusion.1, 2 Blood loss needs to be controlled during surgery to ensure the operation proceeds smoothly, to avoid the risks with blood
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transfusion, and to reduce postoperative complications.3
Volatile anesthetics like isoflurane and sevoflurane are now widely used in
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OMS. Previous research in rabbits showed that isoflurane increased blood flow in the tongue mucosa.4 Another study showed that isoflurane increased blood flow more
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than sevoflurane in the mandibular bone marrow and other oral tissues in rabbits.5 Clinical research has shown that isoflurane increases blood flow in the oral mucosa6
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and sevoflurane reduces microcirculation under the tongue.7 Narcotic analgesics fentanyl and remifentanil are also widely used for pain relief during OMS under general anesthesia. Recent research has shown that, like the volatile anesthetics, these narcotic analgesics also affect oral tissue blood flow. Research in rabbits showed that fentanyl reduced blood flow in the oral mucosa,4 and other studies have suggested that
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ACCEPTED MANUSCRIPT remifentanil may be useful for OMS because it reduces blood flow in the mandibular bone marrow without markedly reducing blood pressure.8,
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Clinical research has
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shown that compared with fentanyl, remifentanil reduces blood loss and allows intraoperative hypotension without serious adverse events.10–12 One study reported that during nasal septal surgery without a concomitant use of remifentanil, blood loss
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was higher with isoflurane than with sevoflurane.13 There are few studies that
anesthesia,14,
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compare blood loss during OMS when remifentanil is used as an adjunct to inhalation and it is unclear what effects the combined use of isoflurane with
strong vasodilating potency and remifentanil have on the blood loss.
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The purpose of this study was to compare blood loss in remifentanil-based anesthesia with inhalation anesthetics anesthetics during orthognathic surgery. We
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hypothesized that blood loss in remifentanil-based anesthesia may be affected based
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on the difference of vasodilative activities of inhalation anesthetics. The specific aim was to compare blood loss in remifentanil-based anesthesia with sevoflurane and that with isoflurane during orthognathic surgery.
Patients and methods
Study design and sample 4
ACCEPTED MANUSCRIPT This study was designed and implemented as a randomized controlled trial. This study was approved by the Tokyo Dental College Ethics Committee (approval number 541).
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We enrolled patients classified as ASA class I or II, aged between 16 years and 50 years, who were scheduled for Le Fort I osteotomy and sagittal split ramus osteotomy of the mandible at the Chiba Hospital of Tokyo Dental College. Written informed
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consent was obtained from all patients or their guardians. Patients with severe heart
Data collection methods
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disease, liver/kidney disease, or muscle disease were excluded from the study.
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The patients enrolled were randomized by using a randomization table before surgery to the sevoflurane group (Sevo group) or the isoflurane group (Iso group). After
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transfer into the operating room, the patients were laid in a horizontal position and venous access was secured using a 20 G catheter inserted into the forearm cephalic
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vein. Anesthesia was induced using 0.01 mg/kg atropine sulfate (up to 0.5 mg/kg), 2 µg/kg fentanyl citrate, and 2 mg/kg propofol. Muscle relaxation was achieved using 0.6 mg/kg rocuronium bromide before nasotracheal intubation was performed. Anesthesia was maintained using 3 L/min air, 1 L/min oxygen, and end-tidal concentrations of 1.4% sevoflurane or 0.9% isoflurane (0.8 MAC for both groups),
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ACCEPTED MANUSCRIPT while muscle relaxation was achieved through continuous administration of 5 µg/kg/min rocuronium bromide. Remifentanil continuously infused at 0.05–0.5
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µg/kg/min to maintain mean blood pressure (MBP) during anesthesia at 60–65 mmHg. When MBP was lower than 60mmHg for more than five minutes, 2-8 mg ephedrine hydrochloride was administered depending on MBP. One percent lidocaine
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solution with 1:100,000 epinephrine was administered to the surgical field. The end-
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tidal carbon dioxide concentration was maintained during anesthesia in both groups at 35–45 mmHg through controlled mechanical ventilation. Acetated Ringer’s solution was administered at 8 mL/kg/h for fluid infusion during surgery. Continuous
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monitoring under anesthesia involved pulse oximetry, non-invasive blood pressure measurement, ECG, invasive arterial pressure measurement via cannulation of the
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radial artery, bispectral index (BIS) measurement, and end-tidal anesthetic gas
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concentrations. Systolic blood pressure (SBP), MBP, diastolic blood pressure (DBP), heart rate (HR), and BIS values were recorded every 5 min and final blood loss (mL/kg) was measured at the end of the surgery. Duration of surgery, duration of anesthesia, fluid infusion volume, mean remifentanil infusion rate (µg/kg/min) were also recorded. When blood hemoglobin concentration at the time of suturing was less
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ACCEPTED MANUSCRIPT than 10g/dL, autologous blood transfusion was started after the measurement of final blood loss.16
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Study variables
The primary outcome variable was blood loss. Demographic variables included age,
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gender, height, weight, body mass index (BMI). Time variables were duration of
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surgery and duration of anesthesia. Surgery/anesthesia-related variables were HR, SBP, MBP, coefficient of variation in mean blood pressure (CVMBP), DBP, remifentanil infusion rate and BIS value. The other variables of interest included total
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volume of local anesthetics, total amount of epinephrine contained in local anesthetic solution, and total amount of ephedrine hydrochloride to improve hypotension. The
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values for HR, SBP, MBP, DBP, and BIS were calculated as mean values during
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surgery. The measurements are expressed as mean ± SD.
Data analyses
Based on the results of a previous study to compare blood loss during orthognathic surgery between sevoflurane and desflurane anesthesia,14 and using α = 0.05 and β = 0.2 for a study design incorporating two groups of equal size, a sample size of 31 patients per group was estimated. Student t-test for unpaired samples was used for 7
ACCEPTED MANUSCRIPT statistical analysis. P < .05 was considered statistically significant. Statistical analysis
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was performed using PASW statistics version 18 (SPSS Inc., Chicago, Illinois).
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ACCEPTED MANUSCRIPT Results
This study was composed of 64 patients. The mean age and male/female ratios were
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25 years (17–50 years) and 10 males, 22 females in the Sevo group and 26 years (16– 47 years) and 9 males, 23 females in the Iso group. No differences were observed
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between the two groups in terms of sex, age, height, weight, BMI, duration of surgery, duration of anesthesia, the total volume of local anesthetics, and the total amount of
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epinephrine (Table 1, 2). Operations were performed by five surgeons, who have adequate experiences of at least 50 cases in orthognathic surgery. Distribution of the surgeons in the two groups was similar. The remifentanil infusion rate (µg/kg/min)
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was significantly lower in the Iso group compared with the Sevo group (P = .004). Total amount of ephedrine hydrochloride administered was significantly higher in the
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Iso group compared with the Sevo group (P = .008) (Table 2). The BIS value was
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significantly lower in the Iso group compared with the Sevo group (P < .001) (Table 3).
Although no significant differences were observed between the groups for intraoperative HR, SBP, MBP, or DBP, CVMBP was significantly higher in the Iso group compared with the Sevo group ( P = .04) (Table 3).
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ACCEPTED MANUSCRIPT Intraoperative blood loss was 4.00 ± 1.98 mL/kg in the Sevo group and 4.79 ± 3.22 mL/kg in the Iso group. Although blood loss tended to be higher in the Iso group,
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intraoperative adverse events were observed in this study.
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there was no significant difference between the two groups (Figure 1). No
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ACCEPTED MANUSCRIPT Discussion
The purpose of this study was to compare blood loss in remifentanil-based anesthesia
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with sevoflurane and that with isoflurane during orthognathic surgery. This study showed that although blood loss tended to be higher in the Iso group compared with
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the Sevo group, the difference was not significant. BIS value under anesthesia was lower in the Iso group compared with the Sevo group. Total amount of ephedrine
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hydrochloride was higher in the Iso group compared with the Sevo group. Mean remifentanil infusion rate was less in the Iso group compared with the Sevo group.
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However, CVMBP was higher in the Iso group compared with the Sevo group.
The combined use of remifentanil with inhalation anesthetics allows sufficient
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pain relief and sedation at a low MAC because of drug interactions.17–19 In the clinical setting, one study reported that anesthesia can be maintained appropriately with
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continuous infusion of remifentanil at 0.1–0.3 µg/kg/min and the inhalation anesthetic maintained at 0.5–0.8 MAC.20 Rossi et al. investigated desflurane or sevoflurane maintained at 0.8 MAC under a concomitant use of 0.5 µg/kg/min remifentanil during orthognathic surgery and reported that blood loss was lower with desflurane anesthesia.14 We drew upon this research in our study to maintain anesthesia with the
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ACCEPTED MANUSCRIPT inhalation anesthetic at 0.8 MAC and remifentanil at 0.05–0.5 µg/kg/min. Blood loss is lower in patients with MBP maintained at 55–65 mmHg compared with those with
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MBP maintained at 75–85 mmHg,21 and that maintaining MBP at 65 mmHg provides appropriate conditions for surgical procedures and reduces blood loss.22 Circulation in vital organs can be maintained safely if MBP is 55 mmHg or above.23 We assumed
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that blood loss could be reduced and systemic circulation safely maintained if
MBP at 60–65 mmHg in this study.
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anesthesia were maintained with MBP at around 65 mmHg. Therefore, we maintained
Research has shown that volatile anesthetics exhibit different BIS values when 25
Olofsen et al. investigated the relationships of
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maintained at the same MAC.24,
isoflurane and sevoflurane concentrations to BIS value and reported that the BIS
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value declined in a concentration-dependent manner up to a certain concentration of
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anesthetic (isoflurane: 0.75% or approx. 0.65 MAC; sevoflurane: 1.5% or approx. 0.9 MAC), and then plateaued at around 40 for higher concentrations.26 The lower BIS value in the Iso group in our study may reflect the change in brainwaves caused by the inhalation anesthetic. However, although the BIS value was within the 40–60 range at the optimal depth of anesthesia, we cannot rule out the possibility that the level of
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ACCEPTED MANUSCRIPT anesthesia was deeper in the Iso group compared with the Sevo group. However, because the objective of our study was to compare blood loss when the inhalation
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anesthetics were maintained at the same MAC and MBP was maintained at around 60 mmHg, we did not correct for differences in BIS value. If we assume that this difference in BIS value affects blood loss, we might expect blood loss to be higher in
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the Sevo group where depth of anesthesia was light, but no difference was observed
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between the two groups in this study. Therefore, we believe that differences in BIS value did not have a major effect in this study.
In addition, the infusion rate of remifentanil in this study may have been less
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in the Iso group compared with the Sevo group because isoflurane dilates the blood vessels in a concentration-dependent manner27 and renders patients more likely to
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develop intraoperative hypotension. According by, blood pressure may have been
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lower during the non-invasive procedures in the Iso group, and the anesthesiologist may have reduced the infusion rate of remifentanil. As a result, more ephedrine hydrochloride was required in the Iso group. The remifentanil dose might then have been insufficient for subsequent invasive surgical procedures, which may explain why CVMBP was larger in the Iso group compared with the Sevo group.
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ACCEPTED MANUSCRIPT Research in rabbits has shown that isoflurane increased tissue blood flow in a concentration-dependent manner in the head and neck region, including bone marrow
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and alveolar tissues in the lower jaw, whereas sevoflurane produced no such change in mandibular bone marrow tissue.5 Özkiris et al. compared blood loss with the use of sevoflurane or isoflurane anesthesia in nasal septal surgery and reported higher blood
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loss with isoflurane. They explained that this occurs because isoflurane is a
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vasodilator that lowers arterial blood pressure in a concentration-dependent manner, and tissue blood flow increases because of vasodilation regardless of low perfusion pressure.13 Based on these studies, we had expected our comparison of anesthesia
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maintained with sevoflurane or isoflurane during surgery in the head and neck region to show higher blood loss with isoflurane because of its potent vasodilatory effect.
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However, no difference in blood loss was seen between the two groups in our study.
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The literature includes research on remifentanil-based anesthesia with desflurane or sevoflurane during orthognathic surgery, and remifentanil-based anesthesia with desflurane or isoflurane during ENT surgery.15, 28 Remifentanil acts to reduce blood flow in an infusion rate-dependent manner at the site involved, such as in mandibular bone marrow tissue.8, 9 Based on previous research in rabbits,5, 9 we estimated blood
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ACCEPTED MANUSCRIPT flow in the mandibular bone marrow tissue and expected blood flow to be around 10% higher in the Iso group compared with the Sevo group. Although we could find a
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tendency towards higher blood loss in the Iso group, the difference between groups was not significant. This suggests that the decrease of blood flow in the mandibular bone marrow tissue induced by remifentanil was greater than the increase of that
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induced by isoflurane, such that any increase in tissue blood flow was suppressed and
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blood loss was not affected. However, CVMBP was higher in the Iso group compared with the Sevo group in our study, which suggests that intraoperative MBP was
loss.
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unstable. This may have been involved at least in part in the large variability of blood
We did not directly measure intraoperative blood flow in the head and neck
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region in our study. Hence, we cannot determine whether changes in local tissue
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blood flow were involved in blood loss variability. The issues will need to be investigated from multifaceted perspectives because it is extremely difficult to measure tissue blood flow in the operative field in humans.
Results from this study suggest that both anesthetics may be safely used for this type of surgery. In clinical consideration, it would be better to use isoflurane
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ACCEPTED MANUSCRIPT considering the low metabolism rate and its cost effectiveness. On the other hand, it would be better to use sevoflurane considering the emergence profile. Further studies
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will be required to compare intraoperative blood loss among three groups including desflurane.
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In conclusion, in a comparison of intraoperative blood loss in remifentanilbased anesthesia with sevoflurane or isoflurane during orthognathic surgery, no
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difference was observed between the two groups. Next research intended for larger patient population to compare blood loss during surgery among isoflurane,
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sevoflurane and desflurane will be required.
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ACCEPTED MANUSCRIPT References
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Chillemi S, Sinardi D, Marino A, et al.: The use of remifentanil for bloodless
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Minerva Anestesisol 68:645, 2002
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surgical field during vertebral disc resection
Carson JI, Altman DG, Duff A, et al.: Risk of bacterial infection associated with
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allogeneic blood transfusion among patients undergoing hip fracture repair.
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Transfusion 39:694, 1999
Precious DS, Splinter W, Bosco D: Induced hypotensive anesthesia for adolescent orthognathic surgery patients. J Oral and Maxillofac Surg 54:680,
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Ichinohe T, Homma Y, Kaneko Y: Mucosal blood flow during various
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intravenous and inhalational anesthetics in the rabbit. Oral Surg Oral Med Oral
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Pathol Oral Radiol Endod 85: 268, 1998
Okamoto S, Matsuura N, Ichinohe T: Effects of the change in concentration of volatile anesthetics on oral tissue blood flow in rabbits. J Jpn Dent Soc Anesthesiol 41:521, 2013
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Homma Y, Kasahara M, Miyachi K, et al.: A comparison of oral submucosal blood flow changes under propofol anesthesia and isoflurane-nitrous oxide
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anesthesia. J Jpn Dent Soc Anesthesiol 26: 219, 1998
Nihal GÖ, Banu A, Meral K, et al.: Comparison of the effects of sevoflurane,
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isoflurane, and desflurane on microcirculation in coronary artery bypass graft
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Maxillofac Surg 67: 1245, 2009
Koshika K, Ichinohe T, Kaneko Y: Dose-dependent remifentanil decreases oral
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tissue blood flow during sevoflurane and propofol anesthesia in rabbits. J Oral
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Maxillofac Surg 69: 2128, 2011
10. Twersky RS, Jamerson B, Warner DS, et al.: Hemodynamics and emergence profile of remifentanil versus fentanyl prospectively compared in a large population of surgical patients. J Clin Anesth 13:407, 2001
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ACCEPTED MANUSCRIPT 11. Kawano H, Manade S, Matsumoto T, et al.: Comparison of intraoperative blood loss during spinal surgery using either remifentanil or fentanyl as an adjuvant to
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general anesthesia. BMC Anesthesiology 13:46, 2013
12. Miłoński J, Zielińska-Bliźniewska H, Golusiński W, et al.: Effects of three
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different types of anaesthesia on perioperative bleeding control in functional
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endoscopic sinus surgery. Eur Arch Otorhinolaryngol 270:2045, 2013
13. Özkiris M, Kapusuz Z, Öztürk S, et al.: The effects of sevoflurane and isoflurane in nasal septal surgery. J Craniofac Surg 24:1376, 2013
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14. Rossi A, Falzetti G, Donati A, et al.: Desflurane versus sevoflurane to reduce blood loss in maxillofacial surgery. J Oral Maxillofac Surg 68:1007, 2010
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15. Caverni V, Rosa G, Pinto G, et al.: Hypotensive anesthesia and recovery of 16:531,
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cognitive function in long-term craniofacial surgery. J Craniofac Surg 2005
16. Ronald DM: Miller’s Anesthesia. 7th Ed. Philadelphia, Churchill Livingstone Elsevier, 2009, pp 1741
17. Lang E, Kapila A, Shlugman D, et al: Reduction of isoflurane minimal alveolar concentration by remifentanil. Anesthesiology 85:721, 1996 19
ACCEPTED MANUSCRIPT 18. Manyam SC, Gupta DK, Johnson KB, et al: Opioid-volatile anesthetic synergy: a response surface model with remifentanil and sevoflurane as prototypes.
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Anesthesiology 105:267, 2006
19. Murouchi T, Yamakage M, Michifuri Y, et al: Usefulness of remifentanil
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anesthesia in oral surgery. J Clin Anesth 32:1167, 2008
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20. Yamakage M, Namiki A: A long-waited ultra-short acting opioid –remifentanil-. J Clin Anesth (Jpn). 29:1739, 2005
21. Lessard MR, Trépanier CA, Baribault JP, et al: Isoflurane-induced hypotension
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in orthognathic surgery. Anesth Analg 69:379,1989
22. Schindler I, Andel H, Leber J, et al: Moderate induced hypotension provides
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satisfactory operating conditions in maxillofacial surgery. Acta Anaesthesiol
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Scand 138:384,1994
23. Choi WS, Samman N: Risks and benefits of deliberate hypotension in anaesthesia: a systematic review. Int J Oral Maxillofac Surg 37:687, 2008
24. Kim JK, Kim DK, Lee MJ: Relationship of bispectral index to minimum alveolar concentration during isoflurane, sevoflurane or desflurane anaesthesia. J Int Med Res 42:130, 2014 20
ACCEPTED MANUSCRIPT 25. Kurehara K, Horiushi T, Takahashi M, et al: Relationship between minimum alveolar concentration and electroencephalpgraphic bispectral index as well as
anesthesia. Masui 50:512, 2001
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spectral edge frequency 95 during isoflurane/epidural or sevoflurane/epidural
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26. Olofsen E, Dahan A: The dynamic relationship between end-tidal sevoflurane and isoflurane concentrations and bispectral index and spectral edge frequency of
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the electroencephalogram. Anesthesiology 90:1345, 1999
27. Eger EI: The pharmacology of isoflurane. Br J Anaesth 56:71s, 1984
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28. Kaygusuz K, Yildirim A, Kol IO, et al: Hypotensive anaesthesia with remifentanil combined with desflurane or isoflurane in tympanoplasty or
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endoscopic sinus surgery: a randomised, controlled trial. J Laryngol Otol
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122:691, 2008
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ACCEPTED MANUSCRIPT Figure legend
Fig. 1
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Comparison of blood loss (mL/kg). Mean blood loss in the Sevo group was 4.00 ± 1.98 mL/kg, and that in the Iso group was 4.79 ± 3.22 mL/kg. There was no
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statistically significant difference between two groups. Data are shown as mean ± SD.
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ACCEPTED MANUSCRIPT Table 1 Demographic variables Iso Group
P value
Sample size (n)
32
32
NA
Age (yr)
24.9 ± 8.4
25.5 ± 8.3
Sex: male
10 (31.3%)
9 (28.1%)
Height (cm)
164.0 ± 6.7
163.4 ± 9.1
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Weight (kg)
56.7 ± 8.2
58.1 ± 12.0
.58
21.6 ± 2.8
.41
21.1 ± 2.3
.76
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Abbreviation: NA, not applicable.
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BMI (kg/m2)
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Sevo Group
Data are presented as mean ± SD. Student t-test for unpaired samples was used for
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statistical analysis.
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ACCEPTED MANUSCRIPT Table 2 Study variables
Iso Group
P value
Duration of surgery (min)
329.6 ± 70.2
341.3 ± 60.2
.47
Duration of anesthesia (min)
386.3 ± 66.0
401.5 ± 60.2
.34
Blood loss (mL/kg)
4.00 ± 1.98
4.79 ± 3.22
.24
Total amount of epinephrine (mg)
Additional use of ephedrine (n)
.82
0.24 ± 0.49
0.24 ± 0.52
.82
12 (38%)
18 (56%)
.21
1.9 ± 2.9
4.8 ± 5.2*
.008
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Total amount of ephedrine (mg)
24.1 ± 5.2
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(mL)
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Total volume of local anesthetics 24.4 ± 4.9
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Sevo Group
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Data are presented as mean ± SD. Student t-test for unpaired samples was used for
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statistical analysis. *Statistically significant difference between two groups (P < .05).
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ACCEPTED MANUSCRIPT Table 3 Surgery/anesthesia-related variables Iso Group
P value
HR (beats/min)
77.2 ± 9.3
80.2 ± 9.6
.22
SBP (mmHg)
99.8 ± 5.8
97.3 ± 5.9
.1
MBP (mmHg)
64.0 ± 4.2
62.3 ± 4.2
.1
9.6 ± 2.2
DBP (mmHg)
remifentanil infusion rate (µg/kg/min)
11.2 ± 3.6*
.04
49.3 ± 3.8
47.5 ± 3.6
.06
0.19 ± 0.06
0.14 ± 0.06*
.004
50.5 ± 6.8
44.1 ± 6.4*
< .001
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BIS value
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)
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CVMBP (
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Sevo Group
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Data are presented as mean ± SD. Student t-test for unpaired samples was used for
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statistical analysis.
*Statistically significant difference between two groups (P < .05).
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ACCEPTED MANUSCRIPT
S0278-2391(15)00408-5
DOI:
10.1016/j.joms.2015.03.076
Reference:
YJOMS 56776
To appear in:
Journal of Oral and Maxillofacial Surgery
Received Date: 22 January 2015 Revised Date:
23 March 2015
Accepted Date: 29 March 2015
Please cite this article as: Wakasugi Y, Matsuura N, Ichinohe T, Intraoperative blood loss during orthognathic surgery: a comparison of remifentanil-based anesthesia with sevoflurane or isoflurane, Journal of Oral and Maxillofacial Surgery (2015), doi: 10.1016/j.joms.2015.03.076. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Original article
remifentanil-based anesthesia with sevoflurane or isoflurane
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Title: Intraoperative blood loss during orthognathic surgery: a comparison of
*Post graduate Student
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and Tatsuya Ichinohe, D.D.S, Ph.D‡
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Authors: Yumiko Wakasugi, D.D.S, Ph.D,* Nobuyuki Matsuura, D.D.S, Ph.D,†
†Senior Assistant Professor
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‡Professor and Chairman
Institution: Department of Dental Anesthesiology, Tokyo Dental College, Chiba,
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261-8502, Japan.
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Corresponding author: Yumiko Wakasugi E-mail: [email protected] Address: Department of Dental Anesthesiology, Tokyo Dental College 1-2-2, Masago, Mihama-ku, Chiba-shi, Chiba, 261-8502, Japan. Int. phone: +81-43-270-3970 Int. fax: +81-43-270-3971
ACCEPTED MANUSCRIPT Abstract
Purpose: The aim of this study was to compare blood loss in remifentanil-based
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anesthesia with sevoflurane or isoflurane during orthognathic surgery.
Patients and Methods: In this randomized controlled clinical trial, patients who were
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scheduled for orthognathic surgery were divided into one of two groups; sevoflurane
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group (Sevo group) and isoflurane group (Iso group). Anesthesia was maintained using end-tidal concentrations of 1.4% sevoflurane or 0.9% isoflurane. Remifentanil was continuously infused at 0.05–0.5 µg/kg/min to maintain mean blood pressure
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(MBP) at 60–65 mmHg. Intraoperative blood loss (mL/kg) was compared. Student ttest for unpaired samples was used for statistical analysis. P < 0.05 was considered
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statistically significant.
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Results: The study sample was composed of 19 men and 45 women (n = 64). The mean age was 25 years (range, 16 to 50 years). Intraoperative blood loss tended to be higher in the Iso group (n = 32) (4.79 ± 3.22 mL/kg) compared with the Sevo group (n = 32) (4.00 ± 1.98 mL/kg), while there was no significant difference between the two groups.
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ACCEPTED MANUSCRIPT Conclusion: In a comparison of intraoperative blood loss in remifentanil-based anesthesia with sevoflurane or isoflurane during orthognathic surgery, no difference
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Key words: blood loss; anesthesia; sevoflurane; isoflurane
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was observed between the two groups.
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ACCEPTED MANUSCRIPT Introduction
Oral and maxillofacial surgery (OMS), and particularly orthognathic surgery, is
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performed in areas of high blood flow including the oral mucosa and bone marrow. Blood loss during surgery can obstruct the visual field, prolong operating times, and
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increase the risk of a blood transfusion.1, 2 Blood loss needs to be controlled during surgery to ensure the operation proceeds smoothly, to avoid the risks with blood
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transfusion, and to reduce postoperative complications.3
Volatile anesthetics like isoflurane and sevoflurane are now widely used in
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OMS. Previous research in rabbits showed that isoflurane increased blood flow in the tongue mucosa.4 Another study showed that isoflurane increased blood flow more
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than sevoflurane in the mandibular bone marrow and other oral tissues in rabbits.5 Clinical research has shown that isoflurane increases blood flow in the oral mucosa6
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and sevoflurane reduces microcirculation under the tongue.7 Narcotic analgesics fentanyl and remifentanil are also widely used for pain relief during OMS under general anesthesia. Recent research has shown that, like the volatile anesthetics, these narcotic analgesics also affect oral tissue blood flow. Research in rabbits showed that fentanyl reduced blood flow in the oral mucosa,4 and other studies have suggested that
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ACCEPTED MANUSCRIPT remifentanil may be useful for OMS because it reduces blood flow in the mandibular bone marrow without markedly reducing blood pressure.8,
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Clinical research has
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shown that compared with fentanyl, remifentanil reduces blood loss and allows intraoperative hypotension without serious adverse events.10–12 One study reported that during nasal septal surgery without a concomitant use of remifentanil, blood loss
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was higher with isoflurane than with sevoflurane.13 There are few studies that
anesthesia,14,
15
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compare blood loss during OMS when remifentanil is used as an adjunct to inhalation and it is unclear what effects the combined use of isoflurane with
strong vasodilating potency and remifentanil have on the blood loss.
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The purpose of this study was to compare blood loss in remifentanil-based anesthesia with inhalation anesthetics anesthetics during orthognathic surgery. We
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hypothesized that blood loss in remifentanil-based anesthesia may be affected based
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on the difference of vasodilative activities of inhalation anesthetics. The specific aim was to compare blood loss in remifentanil-based anesthesia with sevoflurane and that with isoflurane during orthognathic surgery.
Patients and methods
Study design and sample 4
ACCEPTED MANUSCRIPT This study was designed and implemented as a randomized controlled trial. This study was approved by the Tokyo Dental College Ethics Committee (approval number 541).
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We enrolled patients classified as ASA class I or II, aged between 16 years and 50 years, who were scheduled for Le Fort I osteotomy and sagittal split ramus osteotomy of the mandible at the Chiba Hospital of Tokyo Dental College. Written informed
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consent was obtained from all patients or their guardians. Patients with severe heart
Data collection methods
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disease, liver/kidney disease, or muscle disease were excluded from the study.
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The patients enrolled were randomized by using a randomization table before surgery to the sevoflurane group (Sevo group) or the isoflurane group (Iso group). After
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transfer into the operating room, the patients were laid in a horizontal position and venous access was secured using a 20 G catheter inserted into the forearm cephalic
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vein. Anesthesia was induced using 0.01 mg/kg atropine sulfate (up to 0.5 mg/kg), 2 µg/kg fentanyl citrate, and 2 mg/kg propofol. Muscle relaxation was achieved using 0.6 mg/kg rocuronium bromide before nasotracheal intubation was performed. Anesthesia was maintained using 3 L/min air, 1 L/min oxygen, and end-tidal concentrations of 1.4% sevoflurane or 0.9% isoflurane (0.8 MAC for both groups),
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ACCEPTED MANUSCRIPT while muscle relaxation was achieved through continuous administration of 5 µg/kg/min rocuronium bromide. Remifentanil continuously infused at 0.05–0.5
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µg/kg/min to maintain mean blood pressure (MBP) during anesthesia at 60–65 mmHg. When MBP was lower than 60mmHg for more than five minutes, 2-8 mg ephedrine hydrochloride was administered depending on MBP. One percent lidocaine
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solution with 1:100,000 epinephrine was administered to the surgical field. The end-
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tidal carbon dioxide concentration was maintained during anesthesia in both groups at 35–45 mmHg through controlled mechanical ventilation. Acetated Ringer’s solution was administered at 8 mL/kg/h for fluid infusion during surgery. Continuous
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monitoring under anesthesia involved pulse oximetry, non-invasive blood pressure measurement, ECG, invasive arterial pressure measurement via cannulation of the
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radial artery, bispectral index (BIS) measurement, and end-tidal anesthetic gas
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concentrations. Systolic blood pressure (SBP), MBP, diastolic blood pressure (DBP), heart rate (HR), and BIS values were recorded every 5 min and final blood loss (mL/kg) was measured at the end of the surgery. Duration of surgery, duration of anesthesia, fluid infusion volume, mean remifentanil infusion rate (µg/kg/min) were also recorded. When blood hemoglobin concentration at the time of suturing was less
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ACCEPTED MANUSCRIPT than 10g/dL, autologous blood transfusion was started after the measurement of final blood loss.16
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Study variables
The primary outcome variable was blood loss. Demographic variables included age,
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gender, height, weight, body mass index (BMI). Time variables were duration of
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surgery and duration of anesthesia. Surgery/anesthesia-related variables were HR, SBP, MBP, coefficient of variation in mean blood pressure (CVMBP), DBP, remifentanil infusion rate and BIS value. The other variables of interest included total
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volume of local anesthetics, total amount of epinephrine contained in local anesthetic solution, and total amount of ephedrine hydrochloride to improve hypotension. The
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values for HR, SBP, MBP, DBP, and BIS were calculated as mean values during
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surgery. The measurements are expressed as mean ± SD.
Data analyses
Based on the results of a previous study to compare blood loss during orthognathic surgery between sevoflurane and desflurane anesthesia,14 and using α = 0.05 and β = 0.2 for a study design incorporating two groups of equal size, a sample size of 31 patients per group was estimated. Student t-test for unpaired samples was used for 7
ACCEPTED MANUSCRIPT statistical analysis. P < .05 was considered statistically significant. Statistical analysis
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was performed using PASW statistics version 18 (SPSS Inc., Chicago, Illinois).
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ACCEPTED MANUSCRIPT Results
This study was composed of 64 patients. The mean age and male/female ratios were
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25 years (17–50 years) and 10 males, 22 females in the Sevo group and 26 years (16– 47 years) and 9 males, 23 females in the Iso group. No differences were observed
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between the two groups in terms of sex, age, height, weight, BMI, duration of surgery, duration of anesthesia, the total volume of local anesthetics, and the total amount of
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epinephrine (Table 1, 2). Operations were performed by five surgeons, who have adequate experiences of at least 50 cases in orthognathic surgery. Distribution of the surgeons in the two groups was similar. The remifentanil infusion rate (µg/kg/min)
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was significantly lower in the Iso group compared with the Sevo group (P = .004). Total amount of ephedrine hydrochloride administered was significantly higher in the
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Iso group compared with the Sevo group (P = .008) (Table 2). The BIS value was
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significantly lower in the Iso group compared with the Sevo group (P < .001) (Table 3).
Although no significant differences were observed between the groups for intraoperative HR, SBP, MBP, or DBP, CVMBP was significantly higher in the Iso group compared with the Sevo group ( P = .04) (Table 3).
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ACCEPTED MANUSCRIPT Intraoperative blood loss was 4.00 ± 1.98 mL/kg in the Sevo group and 4.79 ± 3.22 mL/kg in the Iso group. Although blood loss tended to be higher in the Iso group,
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intraoperative adverse events were observed in this study.
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there was no significant difference between the two groups (Figure 1). No
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ACCEPTED MANUSCRIPT Discussion
The purpose of this study was to compare blood loss in remifentanil-based anesthesia
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with sevoflurane and that with isoflurane during orthognathic surgery. This study showed that although blood loss tended to be higher in the Iso group compared with
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the Sevo group, the difference was not significant. BIS value under anesthesia was lower in the Iso group compared with the Sevo group. Total amount of ephedrine
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hydrochloride was higher in the Iso group compared with the Sevo group. Mean remifentanil infusion rate was less in the Iso group compared with the Sevo group.
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However, CVMBP was higher in the Iso group compared with the Sevo group.
The combined use of remifentanil with inhalation anesthetics allows sufficient
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pain relief and sedation at a low MAC because of drug interactions.17–19 In the clinical setting, one study reported that anesthesia can be maintained appropriately with
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continuous infusion of remifentanil at 0.1–0.3 µg/kg/min and the inhalation anesthetic maintained at 0.5–0.8 MAC.20 Rossi et al. investigated desflurane or sevoflurane maintained at 0.8 MAC under a concomitant use of 0.5 µg/kg/min remifentanil during orthognathic surgery and reported that blood loss was lower with desflurane anesthesia.14 We drew upon this research in our study to maintain anesthesia with the
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ACCEPTED MANUSCRIPT inhalation anesthetic at 0.8 MAC and remifentanil at 0.05–0.5 µg/kg/min. Blood loss is lower in patients with MBP maintained at 55–65 mmHg compared with those with
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MBP maintained at 75–85 mmHg,21 and that maintaining MBP at 65 mmHg provides appropriate conditions for surgical procedures and reduces blood loss.22 Circulation in vital organs can be maintained safely if MBP is 55 mmHg or above.23 We assumed
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that blood loss could be reduced and systemic circulation safely maintained if
MBP at 60–65 mmHg in this study.
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anesthesia were maintained with MBP at around 65 mmHg. Therefore, we maintained
Research has shown that volatile anesthetics exhibit different BIS values when 25
Olofsen et al. investigated the relationships of
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maintained at the same MAC.24,
isoflurane and sevoflurane concentrations to BIS value and reported that the BIS
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value declined in a concentration-dependent manner up to a certain concentration of
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anesthetic (isoflurane: 0.75% or approx. 0.65 MAC; sevoflurane: 1.5% or approx. 0.9 MAC), and then plateaued at around 40 for higher concentrations.26 The lower BIS value in the Iso group in our study may reflect the change in brainwaves caused by the inhalation anesthetic. However, although the BIS value was within the 40–60 range at the optimal depth of anesthesia, we cannot rule out the possibility that the level of
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ACCEPTED MANUSCRIPT anesthesia was deeper in the Iso group compared with the Sevo group. However, because the objective of our study was to compare blood loss when the inhalation
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anesthetics were maintained at the same MAC and MBP was maintained at around 60 mmHg, we did not correct for differences in BIS value. If we assume that this difference in BIS value affects blood loss, we might expect blood loss to be higher in
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the Sevo group where depth of anesthesia was light, but no difference was observed
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between the two groups in this study. Therefore, we believe that differences in BIS value did not have a major effect in this study.
In addition, the infusion rate of remifentanil in this study may have been less
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in the Iso group compared with the Sevo group because isoflurane dilates the blood vessels in a concentration-dependent manner27 and renders patients more likely to
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develop intraoperative hypotension. According by, blood pressure may have been
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lower during the non-invasive procedures in the Iso group, and the anesthesiologist may have reduced the infusion rate of remifentanil. As a result, more ephedrine hydrochloride was required in the Iso group. The remifentanil dose might then have been insufficient for subsequent invasive surgical procedures, which may explain why CVMBP was larger in the Iso group compared with the Sevo group.
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ACCEPTED MANUSCRIPT Research in rabbits has shown that isoflurane increased tissue blood flow in a concentration-dependent manner in the head and neck region, including bone marrow
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and alveolar tissues in the lower jaw, whereas sevoflurane produced no such change in mandibular bone marrow tissue.5 Özkiris et al. compared blood loss with the use of sevoflurane or isoflurane anesthesia in nasal septal surgery and reported higher blood
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loss with isoflurane. They explained that this occurs because isoflurane is a
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vasodilator that lowers arterial blood pressure in a concentration-dependent manner, and tissue blood flow increases because of vasodilation regardless of low perfusion pressure.13 Based on these studies, we had expected our comparison of anesthesia
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maintained with sevoflurane or isoflurane during surgery in the head and neck region to show higher blood loss with isoflurane because of its potent vasodilatory effect.
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However, no difference in blood loss was seen between the two groups in our study.
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The literature includes research on remifentanil-based anesthesia with desflurane or sevoflurane during orthognathic surgery, and remifentanil-based anesthesia with desflurane or isoflurane during ENT surgery.15, 28 Remifentanil acts to reduce blood flow in an infusion rate-dependent manner at the site involved, such as in mandibular bone marrow tissue.8, 9 Based on previous research in rabbits,5, 9 we estimated blood
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ACCEPTED MANUSCRIPT flow in the mandibular bone marrow tissue and expected blood flow to be around 10% higher in the Iso group compared with the Sevo group. Although we could find a
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tendency towards higher blood loss in the Iso group, the difference between groups was not significant. This suggests that the decrease of blood flow in the mandibular bone marrow tissue induced by remifentanil was greater than the increase of that
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induced by isoflurane, such that any increase in tissue blood flow was suppressed and
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blood loss was not affected. However, CVMBP was higher in the Iso group compared with the Sevo group in our study, which suggests that intraoperative MBP was
loss.
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unstable. This may have been involved at least in part in the large variability of blood
We did not directly measure intraoperative blood flow in the head and neck
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region in our study. Hence, we cannot determine whether changes in local tissue
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blood flow were involved in blood loss variability. The issues will need to be investigated from multifaceted perspectives because it is extremely difficult to measure tissue blood flow in the operative field in humans.
Results from this study suggest that both anesthetics may be safely used for this type of surgery. In clinical consideration, it would be better to use isoflurane
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ACCEPTED MANUSCRIPT considering the low metabolism rate and its cost effectiveness. On the other hand, it would be better to use sevoflurane considering the emergence profile. Further studies
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will be required to compare intraoperative blood loss among three groups including desflurane.
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In conclusion, in a comparison of intraoperative blood loss in remifentanilbased anesthesia with sevoflurane or isoflurane during orthognathic surgery, no
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difference was observed between the two groups. Next research intended for larger patient population to compare blood loss during surgery among isoflurane,
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sevoflurane and desflurane will be required.
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ACCEPTED MANUSCRIPT References
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Chillemi S, Sinardi D, Marino A, et al.: The use of remifentanil for bloodless
2.
Minerva Anestesisol 68:645, 2002
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surgical field during vertebral disc resection
Carson JI, Altman DG, Duff A, et al.: Risk of bacterial infection associated with
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allogeneic blood transfusion among patients undergoing hip fracture repair.
3.
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Transfusion 39:694, 1999
Precious DS, Splinter W, Bosco D: Induced hypotensive anesthesia for adolescent orthognathic surgery patients. J Oral and Maxillofac Surg 54:680,
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1996
Ichinohe T, Homma Y, Kaneko Y: Mucosal blood flow during various
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intravenous and inhalational anesthetics in the rabbit. Oral Surg Oral Med Oral
5.
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Pathol Oral Radiol Endod 85: 268, 1998
Okamoto S, Matsuura N, Ichinohe T: Effects of the change in concentration of volatile anesthetics on oral tissue blood flow in rabbits. J Jpn Dent Soc Anesthesiol 41:521, 2013
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Homma Y, Kasahara M, Miyachi K, et al.: A comparison of oral submucosal blood flow changes under propofol anesthesia and isoflurane-nitrous oxide
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anesthesia. J Jpn Dent Soc Anesthesiol 26: 219, 1998
Nihal GÖ, Banu A, Meral K, et al.: Comparison of the effects of sevoflurane,
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isoflurane, and desflurane on microcirculation in coronary artery bypass graft
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surgery. J Cardiothorac Vasc Anesth 26:791, 2012
Kemmochi M, Ichinohe T, Kaneko Y: Remifentanil decreases mandibular bone marrow blood flow during propofol or sevoflurane anesthesia in rabbits. J Oral
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Maxillofac Surg 67: 1245, 2009
Koshika K, Ichinohe T, Kaneko Y: Dose-dependent remifentanil decreases oral
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tissue blood flow during sevoflurane and propofol anesthesia in rabbits. J Oral
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Maxillofac Surg 69: 2128, 2011
10. Twersky RS, Jamerson B, Warner DS, et al.: Hemodynamics and emergence profile of remifentanil versus fentanyl prospectively compared in a large population of surgical patients. J Clin Anesth 13:407, 2001
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ACCEPTED MANUSCRIPT 11. Kawano H, Manade S, Matsumoto T, et al.: Comparison of intraoperative blood loss during spinal surgery using either remifentanil or fentanyl as an adjuvant to
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general anesthesia. BMC Anesthesiology 13:46, 2013
12. Miłoński J, Zielińska-Bliźniewska H, Golusiński W, et al.: Effects of three
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different types of anaesthesia on perioperative bleeding control in functional
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endoscopic sinus surgery. Eur Arch Otorhinolaryngol 270:2045, 2013
13. Özkiris M, Kapusuz Z, Öztürk S, et al.: The effects of sevoflurane and isoflurane in nasal septal surgery. J Craniofac Surg 24:1376, 2013
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14. Rossi A, Falzetti G, Donati A, et al.: Desflurane versus sevoflurane to reduce blood loss in maxillofacial surgery. J Oral Maxillofac Surg 68:1007, 2010
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15. Caverni V, Rosa G, Pinto G, et al.: Hypotensive anesthesia and recovery of 16:531,
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cognitive function in long-term craniofacial surgery. J Craniofac Surg 2005
16. Ronald DM: Miller’s Anesthesia. 7th Ed. Philadelphia, Churchill Livingstone Elsevier, 2009, pp 1741
17. Lang E, Kapila A, Shlugman D, et al: Reduction of isoflurane minimal alveolar concentration by remifentanil. Anesthesiology 85:721, 1996 19
ACCEPTED MANUSCRIPT 18. Manyam SC, Gupta DK, Johnson KB, et al: Opioid-volatile anesthetic synergy: a response surface model with remifentanil and sevoflurane as prototypes.
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Anesthesiology 105:267, 2006
19. Murouchi T, Yamakage M, Michifuri Y, et al: Usefulness of remifentanil
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anesthesia in oral surgery. J Clin Anesth 32:1167, 2008
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20. Yamakage M, Namiki A: A long-waited ultra-short acting opioid –remifentanil-. J Clin Anesth (Jpn). 29:1739, 2005
21. Lessard MR, Trépanier CA, Baribault JP, et al: Isoflurane-induced hypotension
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in orthognathic surgery. Anesth Analg 69:379,1989
22. Schindler I, Andel H, Leber J, et al: Moderate induced hypotension provides
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satisfactory operating conditions in maxillofacial surgery. Acta Anaesthesiol
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Scand 138:384,1994
23. Choi WS, Samman N: Risks and benefits of deliberate hypotension in anaesthesia: a systematic review. Int J Oral Maxillofac Surg 37:687, 2008
24. Kim JK, Kim DK, Lee MJ: Relationship of bispectral index to minimum alveolar concentration during isoflurane, sevoflurane or desflurane anaesthesia. J Int Med Res 42:130, 2014 20
ACCEPTED MANUSCRIPT 25. Kurehara K, Horiushi T, Takahashi M, et al: Relationship between minimum alveolar concentration and electroencephalpgraphic bispectral index as well as
anesthesia. Masui 50:512, 2001
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spectral edge frequency 95 during isoflurane/epidural or sevoflurane/epidural
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26. Olofsen E, Dahan A: The dynamic relationship between end-tidal sevoflurane and isoflurane concentrations and bispectral index and spectral edge frequency of
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the electroencephalogram. Anesthesiology 90:1345, 1999
27. Eger EI: The pharmacology of isoflurane. Br J Anaesth 56:71s, 1984
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28. Kaygusuz K, Yildirim A, Kol IO, et al: Hypotensive anaesthesia with remifentanil combined with desflurane or isoflurane in tympanoplasty or
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endoscopic sinus surgery: a randomised, controlled trial. J Laryngol Otol
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122:691, 2008
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ACCEPTED MANUSCRIPT Figure legend
Fig. 1
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Comparison of blood loss (mL/kg). Mean blood loss in the Sevo group was 4.00 ± 1.98 mL/kg, and that in the Iso group was 4.79 ± 3.22 mL/kg. There was no
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statistically significant difference between two groups. Data are shown as mean ± SD.
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ACCEPTED MANUSCRIPT Table 1 Demographic variables Iso Group
P value
Sample size (n)
32
32
NA
Age (yr)
24.9 ± 8.4
25.5 ± 8.3
Sex: male
10 (31.3%)
9 (28.1%)
Height (cm)
164.0 ± 6.7
163.4 ± 9.1
.76
Weight (kg)
56.7 ± 8.2
58.1 ± 12.0
.58
21.6 ± 2.8
.41
21.1 ± 2.3
.76
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Abbreviation: NA, not applicable.
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BMI (kg/m2)
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Sevo Group
Data are presented as mean ± SD. Student t-test for unpaired samples was used for
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statistical analysis.
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ACCEPTED MANUSCRIPT Table 2 Study variables
Iso Group
P value
Duration of surgery (min)
329.6 ± 70.2
341.3 ± 60.2
.47
Duration of anesthesia (min)
386.3 ± 66.0
401.5 ± 60.2
.34
Blood loss (mL/kg)
4.00 ± 1.98
4.79 ± 3.22
.24
Total amount of epinephrine (mg)
Additional use of ephedrine (n)
.82
0.24 ± 0.49
0.24 ± 0.52
.82
12 (38%)
18 (56%)
.21
1.9 ± 2.9
4.8 ± 5.2*
.008
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Total amount of ephedrine (mg)
24.1 ± 5.2
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(mL)
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Total volume of local anesthetics 24.4 ± 4.9
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Sevo Group
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Data are presented as mean ± SD. Student t-test for unpaired samples was used for
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statistical analysis. *Statistically significant difference between two groups (P < .05).
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ACCEPTED MANUSCRIPT Table 3 Surgery/anesthesia-related variables Iso Group
P value
HR (beats/min)
77.2 ± 9.3
80.2 ± 9.6
.22
SBP (mmHg)
99.8 ± 5.8
97.3 ± 5.9
.1
MBP (mmHg)
64.0 ± 4.2
62.3 ± 4.2
.1
9.6 ± 2.2
DBP (mmHg)
remifentanil infusion rate (µg/kg/min)
11.2 ± 3.6*
.04
49.3 ± 3.8
47.5 ± 3.6
.06
0.19 ± 0.06
0.14 ± 0.06*
.004
50.5 ± 6.8
44.1 ± 6.4*
< .001
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BIS value
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)
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CVMBP (
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Sevo Group
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Data are presented as mean ± SD. Student t-test for unpaired samples was used for
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statistical analysis.
*Statistically significant difference between two groups (P < .05).
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