Effect of Different Doses of Ciprofol on Hemodynamics Induced By General Anesthesia in Elderly Diabetic Patients Undergoing Spinal Surgery: A double-blind, randomized, controlled study

Effect of Different Doses of Ciprofol on Hemodynamics Induced By General Anesthesia in Elderly Diabetic Patients Undergoing Spinal Surgery: A double-blind, randomized, controlled study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect of Different Doses of Ciprofol on Hemodynamics Induced By General Anesthesia in Elderly Diabetic Patients Undergoing Spinal Surgery: A double-blind, randomized, controlled study Xiao-rui Jiang, Lin-zhong Zhang, Jia-wei Ji, Yan Jing, Mei-ping Li This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5089178/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Jan, 2025 Read the published version in BMC Anesthesiology → Version 1 posted 4 You are reading this latest preprint version Abstract Objective To investigate the safety and efficacy of different doses ciprofol in induction of general anesthesia in elderly diabetic patients. Methods Ninety spinal single-level PLIF patients who were planned to undergo elective tracheal intubation under general anesthesia were selected as the subjects.The study subjects were randomly divided into 3 groups. Ciprofol induction dose was 0.2 mg/kg in group A, 0.3 mg/kg in group B and 0.4 mg/kg in group C, The safety and efficacy of general anesthesia induction were compared among the three groups. Results The incidence of hypotension in group C (46.4%) was significantly higher than that in group A (7.4%) and group B (14.8%) (P < 0.05). AUCMAP of the three groups was higher in group C (176.39±33.83 mmHg.min) than in group B (158.44±26.55 mmHg.min) and higher in group B than in group A (143.59±19.52 mmHg.min), P < 0.05. The incidence of intubation reaction in group A (77.8%) was the highest (P < 0.05). There were significant differences in BIS values at 3, 4 and 5 minutes after administration. Conclusion The use of 0.3mg/kg ciprofol in the induction period in elderly diabetic patients has more stable circulation and less vasoactive drug dosage during induction, which is better than 0.2 and 0.4mg/kg dosage groups. The trial was registered at Chinese ClinicalTrials.gov in February 26, 2024 (Registration number:ChiCTR2400081164). Older adults Diabetes mellitus ciprofol General anesthesia induction Figures Figure 1 Figure 2 Introduction With the aging of society, more and more elderly people need to undergo general anesthesia surgery. Elderly patients often have multiple complications, and the risk of surgical complications is relatively increased [1]. General anaesthesia induced hypotension is very common and associated with poor prognosis [2]. Its risk factors include: elderly patients, history of hypertension, ASA III-V, type 2 diabetes, and propofol induction [3-4]. Cyclopofol is a new sedative anesthetic independently developed in China, which has a low incidence of adverse reactions such as hypotension, bradycardia and respiratory depression [5]. At present, the commonly used dose is 0.4 mg/kg, which can be safely used for short operations such as painless gastroenteroscopy, bronchoscopy, and endoscopic retrograde cholangiopancreatography [6-7]. A number of studies have shown that cyclopofol can also be safely and effectively used for induction and maintenance of general anesthesia, and the dosage range is 0.4~0.9 mg/kg, and compared with propofol, cardiovascular adverse events are significantly reduced, and blood pressure and heart rate are less increased. Li et al. [8] studied the potential effects of dose and age on the pharmacokinetic characteristics and safety of cyclopofol, and believed that the dosage of 0.3 mg/kg of cyclopofol should be selected for clinical use in elderly patients. Elderly diabetic patients are sensitive to anesthetic drugs, have weak compensatory capacity, and are prone to cardiovascular and cerebrovascular accidents, so the dose and safety of the drug need to be further evaluated. The purpose of this study was to investigate the safety and effectiveness of different doses of cyclopofol in the induction of general anesthesia in elderly diabetic patients, and to provide reference for clinical work. Data and methods 1.1 General Information The present prospective, double-blind, single-center study was conducted at The Second hospital of Shanxi Medical University Hospital. This study was approved by the Ethics Committee of the Second Hospital of Shanxi Medical University (review board number [2024] YX 021), and patients or their families signed informed consent. Select data and methods from 2024.2-2024.6. The trial was registered at Chinese ClinicalTrials.gov in 26/02/2024(Registration number:ChiCTR2400081164). Written informed consent was obtained from all participants. Tis manuscript adheres to the applicable EQUATOR guidelines. 1.1 General Information Patients with spinal single-level PLIF operation who were hospitalized in the Second Clinical College of Shanxi Medical University from 2024.2-2024.6 and planned to undergo elective tracheal intubation under general anesthesia were selected as the study objects. According to the results of previous studies, we assumed that the significance level α was 0.05 and the test efficacy 1-β was 0.9. The sample size was calculated to be 70 cases, and the sample size was increased to 90 cases considering the factors such as loss of follow-up. SPSS 26.0 software was used to generate random numbers, and the study subjects were randomly divided into 3 groups. The induced dose of cyclopofol was 0.2 mg/kg in group A, 0.3 mg/kg in group B, and 0.4 mg/kg in group C. 1.2 Inclusion criteria: (1) Diabetic patients (all of whom were clearly diagnosed by secondary and above public hospitals); (2) Age ≥65 years old; (3) ASA grade Ⅱ-Ⅲ; (4) BMI: 18-30 kg/m2 (5) Selected patients who received general anesthesia tracheal intubation lumbar PLIF (single level). 1.3 Exclusion criteria: cyclopofol allergy, abnormal liver and kidney function, bradycardia (heart rate < 60 beats/min), hypotension (mean arterial pressure < 55 mmhg), prolonged QT interval, could not cooperate with researchers. After assessing patient eligibility, they were informed regarding the study by members of the study team, with written informed consent then being obtained. 1.4 Research Methods After the patient was admitted, peripheral venous channels were opened and ECG monitoring was performed. HR, BP, ECG, SpO2, RR, BIS were monitored. Radial artery puncture catheters were placed under 2% lidocaine 2 ml local anesthesia, invasive arterial pressure was monitored, and blood glucose (T0) was measured. After the invasive arterial pressure monitoring operation was completed, nasal catheter oxygen was administered for 2 L/min, midazolam was given 0.02 mg/kg, and intravenous injection was given slowly. When the patient's sedation score (Ramsay score) was 3, blood pressure and heart rate at this time were recorded as the basic blood pressure and basic heart rate. Oxygen was absorbed in the mask for 5 L/min, and after full pre-oxygenation, Sufentanil 0.4ug /kg and cyclopofol were given successively (0.2mg /kg in group A, 0.3mg /kg in group B and 0.4mg /kg in group C, all diluted to 20 ml by 0.9% sodium chloride solution) for 30s. After the patient's eyelash reflex disappeared, rocuronium 0.7 mg/kg was injected, and the observation indicators were recorded. If BIS is still greater than 60 after 5 minutes of induction, propofol 0.5 mg/kg remedial therapy is given (and the case is excluded). Tracheal intubation was performed after successful induction (visual laryngoscope was used; successful intubation was required once; unsuccessful cases were excluded), and blood glucose (T1) was monitored 2min after intubation and intubation reaction was recorded. After intubation, a ventilator was connected for assisted ventilation. Respiratory parameters were set as follows: oxygen flow rate of 2 L/min, tidal volume of 6-8 ml/kg, respiratory rate of 10-14 times /min, suction/breath ratio of 1:2, and PetCO2 was maintained between 30-40 mmHg. Propofol 4-12 mg·kg-1·h-1 and reifentanil 8-15ug·kg-1·min-1 were selected for anesthesia maintenance, and the drug concentration was adjusted so that BIS fluctuated between 40-60. During the operation, the anesthesiologist added analgesia and muscle relaxants according to the patient's conditions, such as hypotension and bradycardia. The anesthesiologist selects vasoactive drugs according to the patient's condition. After the operation, after the patient became conscious, the cough reflex recovered, and breathing returned to normal (VT>6 mL/kg, respiratory rate >10 times /min, end-tidal CO2 (ETCO2) <45 mmHg), the tracheal catheter was removed and sent to PACU. All of the above procedures are performed by a professional anesthesiologist. 1.5 Observation Indicators 1.5.1 Main outcome measures: Incidence of hypotension at induction of anesthesia (mean arterial pressure < 55 mmhg and lasting for at least one minute). 1.5.2 Minor Observation Indicators: Area under the curve (AUCMAP) of blood pressure below BBP during anesthesia induction, incidence of bradycardia (heart rate < 50 beats/min), area under the curve of heart rate below BHR (AUCHR), time to disappearance of eyelash reflexia, time for BIS to drop to 60, intubation response (within 3 minutes after intubation, Systolic blood pressure, diastolic blood pressure, or heart rate > 20% of the baseline value), the number of intraoperative hypotension episodes, the number of vasoactive drugs used, the dosage of pressors, and the blood glucose levels at 2 minutes after entry and intubation. 1.6 Statistical Methods SPSS 26.0 software was used for statistical analysis. The measurement data of normal distribution were expressed as mean ± standard deviation (), and ANOVA was used for inter-group comparison. The measurement data of the non-normal distribution were expressed as the median (interquartile distance), and the multiple local rank sum test was used for inter-group comparison. The count data were expressed as rate (%), and the Chi-square test or Fisher exact probability method were used for comparison between groups. P < 0.05 was considered statistically significant. Patients with spinal single-level PLIF who were admitted to the Second Clinical College of Shanxi Medical University and planned to undergo elective tracheal intubation under general anesthesia were studied. According to the results of previous studies, we assumed that the significance level α was 0.05 and the test efficacy 1-β was 0.9. The sample size was calculated to be 70 cases, and the sample size was increased to 90 cases considering the factors such as loss of follow-up. SPSS 26.0 software was used to generate random numbers, and the study subjects were randomly divided into 3 groups. The induced dose of cyclopofol was 0.2 mg/kg in group A, 0.3 mg/kg in group B, and 0.4 mg/kg in group C. 1.2 Inclusion criteria: (1) Diabetic patients (all of whom were clearly diagnosed by secondary and above public hospitals); (2) Age ≥65 years old; (3) ASA grade Ⅱ-Ⅲ; (4) BMI: 18-30 kg/m2 (5) Selected patients who received general anesthesia tracheal intubation lumbar PLIF (single level). 1.3 Exclusion criteria: cyclopofol allergy, abnormal liver and kidney function, bradycardia (heart rate < 60 beats/min), hypotension (mean arterial pressure < 55 mmhg), prolonged QT interval, could not cooperate with researchers. 1.4 Research Methods After the patient was admitted, peripheral venous channels were opened and ECG monitoring was performed. HR, BP, ECG, SpO2, RR, BIS were monitored. Radial artery puncture catheters were placed under 2% lidocaine 2 ml local anesthesia, invasive arterial pressure was monitored, and blood glucose (T0) was measured. After the invasive arterial pressure monitoring operation was completed, nasal catheter oxygen was administered for 2 L/min, midazolam was given 0.02 mg/kg, and intravenous injection was given slowly. When the patient's sedation score (Ramsay score) was 3, blood pressure and heart rate at this time were recorded as the basic blood pressure and basic heart rate. Oxygen was absorbed in the mask for 5 L/min, and after full pre-oxygenation, Sufentanil 0.4ug /kg and cyclopofol were given successively (0.2mg /kg in group A, 0.3mg /kg in group B and 0.4mg /kg in group C, all diluted to 20 ml by 0.9% sodium chloride solution) for 30s. After the patient's eyelash reflex disappeared, rocuronium 0.7 mg/kg was injected, and the observation indicators were recorded. If BIS is still greater than 60 after 5 minutes of induction, propofol 0.5 mg/kg remedial therapy is given (and the case is excluded). Tracheal intubation was performed after successful induction (visual laryngoscope was used; successful intubation was required once; unsuccessful cases were excluded), and blood glucose (T1) was monitored 2min after intubation and intubation reaction was recorded. After intubation, a ventilator was connected for assisted ventilation. Respiratory parameters were set as follows: oxygen flow rate of 2 L/min, tidal volume of 6-8 ml/kg, respiratory rate of 10-14 times /min, suction/breath ratio of 1:2, and PetCO2 was maintained between 30-40 mmHg. Propofol 4-12 mg·kg-1·h-1 and reifentanil 8-15ug·kg-1·min-1 were selected for anesthesia maintenance, and the drug concentration was adjusted so that BIS fluctuated between 40-60. During the operation, the anesthesiologist added analgesia and muscle relaxants according to the patient's conditions, such as hypotension and bradycardia. The anesthesiologist selects vasoactive drugs according to the patient's condition. After the operation, after the patient became conscious, the cough reflex recovered, and breathing returned to normal (VT>6 mL/kg, respiratory rate >10 times /min, end-tidal CO2 (ETCO2) <45 mmHg), the tracheal catheter was removed and sent to PACU. All of the above procedures are performed by a professional anesthesiologist. 1.5 Observation Indicators 1.5.1 Main outcome measures: Incidence of hypotension at induction of anesthesia (mean arterial pressure < 55 mmhg and lasting for at least one minute). 1.5.2 Minor Observation Indicators: Area under the curve (AUCMAP) of blood pressure below BBP during anesthesia induction, incidence of bradycardia (heart rate < 50 beats/min), area under the curve of heart rate below BHR (AUCHR), time to disappearance of eyelash reflexia, time for BIS to drop to 60, intubation response (within 3 minutes after intubation, Systolic blood pressure, diastolic blood pressure, or heart rate > 20% of the baseline value), the number of intraoperative hypotension episodes, the number of vasoactive drugs used, the dosage of pressors, and the blood glucose levels at 2 minutes after entry and intubation. 1.6 Statistical Methods SPSS 26.0 software was used for statistical analysis. The measurement data of normal distribution were expressed as mean ± standard deviation (), and ANOVA was used for inter-group comparison. The measurement data of the non-normal distribution were expressed as the median (interquartile distance), and the multiple local rank sum test was used for inter-group comparison. The count data were expressed as rate (%), and the Chi-square test or Fisher exact probability method were used for comparison between groups. P < 0.05 was considered statistically significant. Results 2.1 Comparison of general conditions of patients in the three groups A total of 90 patients were included in this study, among which 6 patients were excluded due to unsuccessful first intubation, 2 patients were excluded due to the need for propofol remediation, and the remaining 82 patients completed the study, as shown in Figure 1. There was no statistical significance in the comparison of general data among the three groups (P<0.05), as shown in Table 1. 2.2 Hemodynamic comparison among the three groups, the incidence of hypotension in group C was the highest, and the difference was statistically significant compared with group A and Group B. Although group B was higher than group A, the difference was not statistically significant. AUCMAP showed that group C was higher than group B and group B was higher than group A, and the difference was statistically significant. The incidence of bradycardia in group C was the highest, and the difference was statistically significant compared with group A. Compared with the three groups, the AUCHR of group C was greater than that of group B and that of group A, but only the difference between group A and group C was statistically significant. The incidence of intubation reaction in group A was the highest, and the difference was statistically significant compared with the other two groups (see Table 2). 2.3 The sedation effect of patients in the three groups was compared with the disappearance time of eyelash reflex, the time required for BIS to drop to 60, the blood sugar value at two time points, and the frequency of intraoperative hypotension. There were no statistically significant differences among the three groups (see Table 2). However, the lowest BIS value was found in group C, which showed A statistically significant difference compared with group A and B. The change trend of BIS showed that the BIS reached the lowest value in about 1 minute and then rose slowly. Although the BIS values were all less than 60, the BIS values in group A were higher than those in group B and group C at the 3rd, 4th and 5th minute, and the difference was statistically significant. Table 1 Comparison of general conditions among the three groups Group A （n=27） Group B （n=27） Group C （n=28） P Gender (Male) 14（27） 16（27） 14（28） 0.768 0.527 Age (years) 71.33±4.09 69.59±3.87 71.96±3.87 0.076 2.658 BMI（km/m 2 ） 22.72（2.66） 22.68（2.41） 23.29（1.66） 0.575 1.106 ASA（Ⅱ） 13（27） 17（27） 14（28） 0.492 1.420 Duration of diabetes (years) 6.00（8.00） 7.00（8.00） 6.50（10.00） 0.931 0.143 Combined hypertension 18（27） 13（27） 16（28） 0.370 1.990 Complicated with coronary heart disease 12（27） 12（27） 8（28） 0.377 1.952 Basal mean arterial pressure(mmHg) 98.37±4.84 97.63±4.72 99.64±6.71 0.396 0.937 Basal heart rate (times/min) 68.93±4.92 71.67±5.48 72.29±5.45 0.051 3.092 Blood sugar levels at the time of entry 6.34±0.79 6.06±0.72 6.15±0.58 0.320 1.155 Operation duration（min） 138.78±13.23 139.37±17.40 143.32±17.22 0.524 0.652 Anesthesia duration （min） 188.96±14.73 186.78±13.82 188.32±16.55 0.861 0.150 Liquid intake（ml） 1600（500） 1750（500） 1750（500） 0.764 0.538 Amount of bleeding（ml） 190（40） 210（60） 190（50） 0.921 0.165 Table 2 Comparison of induction conditions among the three groups Group A Group B Group C P Hypotension 2（7.4%） 4（14.8%） 14 ab （46.4%） 0.001 13.336 AUC MAP 143.59±19.52 158.44±26.55 a 176.39±33.83 ab 0.000 10.21 Bradycardia 5（18.5%） 8（29.6%） 15 a （53.6%） 0.019 7.876 AUC HR 63.52±19.24 80.26±25.97 a 96.25±26.54 ab 0.000 12.60 AUC BIS 191.15±11.39 204.67±10.40 a 208.43±12.60 a 0.000 17.00 Intubation reaction 21（77.8%） 4（14.8%） a 2（7.1%） a 0.000 37.032 Eyelash reflexes disappear time 57.85±7.52 56.70±6.58 57.25±10.46 0.839 0.176 Time for BIS drop to 60 66.59±8.52 67.07±7.30 68.11±9.14 0.790 33.049 Blood sugar levels after intubation 8.03±0.52 7.88±0.57 7.82±0.48 0.322 1.150 Note: Compared with group A, aP<0.05, compared with group B, bP<0.05 Table 3 Comparison of intraoperative hypotension among the three groups A组 B组 C组 P值 Frequency of intraoperative hypotension 5（2） 5（1） 4（2） 0.778 Pressors were used during the operation ephedrine（mg） 18（6） 18（6） 12（6） 0.228 dopamine（mg） 3（4） 2.5（3.75） 5（3.75） ab 0.012 Note: Compared with group A, aP<0.05, compared with group B, bP<0.05 Discussion This study compared the effects of different doses of cyclopofol on hemodynamics and anesthetic effects of total intoxication induction in elderly diabetic patients. The type of surgery selected was single-stage spinal PILF surgery, because this surgery is a programmed surgery with relatively fixed operation time and blood loss, which can reduce the influence of surgery on hemodynamics. This study found that 0.4 mg/kg cyclopofol combined with 0.4 ug/kg sufentanil and 0.7 mg/kg rocuronium had a higher incidence of hypotension during induction than 0.3 mg/kg and 0.2 mg/kg groups, and the difference was statistically significant. Previous studies [9] also found that 0.4mg /kg cyclopofol induced hypotension had a high probability (57%), which was higher than 46.4% in this study. This may be because hypotension was defined in this study as MAP < 60 mmHg or 30% of the basic blood pressure, while the definition of hypotension in this study was MAP < 55 mmHg. Last 1 minute. Two retrospective studies [10-11] found that intraoperative MAP less than 55 mmHg was associated with AKI and myocardial damage even if the duration was shorter, so hypotension was defined in this study as MAP less than 55 mmHg lasting 1 minute. The use of the subthreshold area method [12], while taking into account the duration and severity of the blood pressure drop, can more fully reflect the situation of blood pressure at induction, and thus better assess the harm of hypotension. Therefore, this study compared the area of MAP lower than the basic value during induction among all groups, and found that the 0.4 mg/kg group was higher than the 0.3 mg/kg and 0.2 mg/kg groups, and the 0.3 mg/kg group was higher than the 0.2 mg/kg group, and the difference was statistically significant. Although there was no statistically significant difference in the incidence of hypotension between the 0.3 and 0.2 groups, AUCMAP in the 0.2 mg group was significantly lower than that in the 0.3 mg group, indicating that the effect of induction on blood pressure in the 0.2 mg group was lower. This study described that the change of heart rate in each group was consistent with the change of blood pressure, indicating that induction in the 0.2 mg/kg group had the least effect on blood pressure and heart rate. This study also found that although there was no statistical significance in the disappearance time of eyelash reflex and the reduction time of BIS below 60 in the 0.2 mg group compared with the other two groups, and the BIS was always lower than 60, the intubation response of the 0.2 mg/kg group was significantly higher than that of the other two groups. At the same time, this study found that the area under the curve of BIS in group A was lower than that in groups B and C, and the BIS value at 3, 4 and 5 minutes after induction in group A was higher than that in the other two groups. However, hypertension and tachycardia caused by intubation response are risk factors for myocardial infarction and stroke [13-14], which is a particular concern for elderly patients and patients with a history of myocardial infarction or stroke [15-17]. Therefore, it is very important to prevent hemodynamic fluctuations of tracheal intubation. Therefore, although previous studies believed that 0.2 mg/kg cyclopofol could meet the demand for sedation during induction, which was consistent with the results of this study, this study found that this group had a high incidence of intubation reaction and was not suitable for elderly diabetic patients. The blood glucose of the three groups was the highest in group A at 2 minutes after intubation, but the difference was not statistically significant. The reason for the increase of blood glucose in group A may be related to the intubation response, and the difference was not statistically significant at present, which may be related to the sample size. There was no statistically significant difference in the number of intraoperative hypotension occurrence and ephedrine dosage among the three groups, but the 0.4mg dopamine dosage group was significantly higher than the other two groups (Table 3), which may be related to the medication habits of researchers. Ephedrine is usually used to treat hypotension. When ephedrine is not effective for a single treatment, dopamine will continue to be injected. Therefore, the failure to observe more intraoperative hypotension in patients in the 0.4 mg group may be related to the pumping of dopamine, which can also indicate that the 0.4 mg group has a greater impact on intraoperative blood pressure. This trial was a single-center trial with a small sample size, and the clinical outcome indicators (such as the incidence of postoperative cardiovascular events and cerebrovascular events, etc.) of the three groups of patients were not observed. After that, a large-sample multi-center clinical trial is needed to reach a more comprehensive conclusion. In summary, 0.3 mg/kg cypofol in the induction period of elderly diabetic patients has more stable circulation and less vasoactive drug dosage during induction, which is better than 0.2 and 0.4 mg/kg dosage groups. Declarations Author’s Contribution Jiang Xiaorui: Design paper, draft paper, write paper; Zhang Linzhong: experimental design, paper modification; Jiang Xiaorui, JI Jiawei, Jing Yan: Research process implementation and data collection; Li Meiping: Data analysis. All authors read and approved the final manuscript and agreed to publish it. Acknowledgements The authors would like to thank all the reviewers who participated in the review and MJEditor (www. mjedi tor. com) for its linguistic assistance during the preparation of this manuscript. Funding This work was supported by the grants from Department of Science and Technology of Shanxi Province (Grant ID:201701D121139) and Beijing Health Alliance Charitable Foundation(grant ID: YXHA-ARP-006). Availability of data and materials The data that support the fndings of this study are available from the corresponding author, Lin-zhong Zhang, upon reasonable request. 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Effect of laryngoscopy and intubation on plasma catecholamine levels during intravenous induction of anaesthesia[J]. Br J Anaesth. 1972;44:1323–8. 10.1093/bja/44.12.1323 . Shribman AJ, Smith G, Achola KJ. Cardiovascular and catecholamine responses to laryngoscopy with and without tracheal intubation[J]. Br J Anaesth. 1987;59:295–9. 10.1093/bja/59.3.295 . Forbes AM, Dally FG. Acute hypertension during induction of anaesthesia and endotracheal intubation in normotensive man. Br J Anaesth. 1970;42:618–24. 10.1093/bja/42.7.618 . Bullington J, Mouton Perry SM, Rigby J, et al. The effect of advancing age on the sympathetic response to laryngoscopy and tracheal intubation. Anesth Analg. 1989;68:603–8. Tomori Z, Widdicombe JG. Muscular, bronchomotor and cardiovascular reflexes elicited by mechanical stimulation of the respiratory tract. J Physiol. 1969;200:25–49. 10.1113/jphysiol.1969.sp008680 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 20 Jan, 2025 Read the published version in BMC Anesthesiology → Version 1 posted Editorial decision: Revision requested 26 Sep, 2024 Editor assigned by journal 24 Sep, 2024 Submission checks completed at journal 24 Sep, 2024 First submitted to journal 14 Sep, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5089178","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":359495892,"identity":"dc42cf87-10c1-4c27-987e-cf37890c5451","order_by":0,"name":"Xiao-rui Jiang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYBAC+/bmA8Y/DNjqG9sbiNRiwHMsoZihgI+xuecAsVokcgw+M3yQY2yfkUCkFnOJBMPNBQZmzLwzH2+8wVBjE01Qi2XPg2TjGQZpbJKz04otGI6l5TYQ1HM84ZgBj8ExHsPZOWYSjA2HidByILH9B4/Bfwn7m2eI1GJwIpnBmMeAzYBxBg+RWiR7jjEYzjBgS2DsAfolgRi/8LP3fzD48Aeopf3wxhsfamyI8AuyIyUSSFEO0UKqjlEwCkbBKBgZAAAVrkGFMolJMQAAAABJRU5ErkJggg==","orcid":"","institution":"The Second hospital of Shanxi Medical University","correspondingAuthor":true,"prefix":"","firstName":"Xiao-rui","middleName":"","lastName":"Jiang","suffix":""},{"id":359495893,"identity":"74645431-db90-4ade-9b18-41b2043e917d","order_by":1,"name":"Lin-zhong Zhang","email":"","orcid":"","institution":"The Second hospital of Shanxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lin-zhong","middleName":"","lastName":"Zhang","suffix":""},{"id":359495896,"identity":"d6d5623a-9651-46ee-95fc-d8aa6d831c92","order_by":2,"name":"Jia-wei Ji","email":"","orcid":"","institution":"The Second hospital of Shanxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jia-wei","middleName":"","lastName":"Ji","suffix":""},{"id":359495898,"identity":"934db8f8-cc91-4d56-bccb-e2c67112dfc2","order_by":3,"name":"Yan Jing","email":"","orcid":"","institution":"The Second hospital of Shanxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Jing","suffix":""},{"id":359495899,"identity":"e349aec6-e1c6-4515-ad64-f4078219c2b6","order_by":4,"name":"Mei-ping Li","email":"","orcid":"","institution":"The Second hospital of Shanxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Mei-ping","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2024-09-14 12:41:38","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5089178/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5089178/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12871-024-02881-3","type":"published","date":"2025-01-20T15:57:22+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":71507146,"identity":"4288ba24-a7eb-4513-96e4-a9349dbb0db7","added_by":"auto","created_at":"2024-12-16 09:54:41","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":438292,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5089178/v1/2977a089223043b26f4e8cd6.jpeg"},{"id":71507764,"identity":"32995330-f3dd-48d9-a11a-9ed92de4df16","added_by":"auto","created_at":"2024-12-16 10:02:41","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":29640,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of BIS at different time points among the three groups\u003c/p\u003e","description":"","filename":"20241216151103.png","url":"https://assets-eu.researchsquare.com/files/rs-5089178/v1/53c6f95adb0d85bf064cdd5e.png"},{"id":74858340,"identity":"bd8b7a3a-ed7f-4bfa-8777-12b8e815ac8b","added_by":"auto","created_at":"2025-01-27 16:08:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":941629,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5089178/v1/86e325ee-9cb5-464f-820c-c63f7f96e97a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of Different Doses of Ciprofol on Hemodynamics Induced By General Anesthesia in Elderly Diabetic Patients Undergoing Spinal Surgery: A double-blind, randomized, controlled study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eWith the aging of society, more and more elderly people need to undergo general anesthesia surgery. Elderly patients often have multiple complications, and the risk of surgical complications is relatively increased [1]. General anaesthesia induced hypotension is very common and associated with poor prognosis [2]. Its risk factors include: elderly patients, history of hypertension, ASA III-V, type 2 diabetes, and propofol induction [3-4].\u003c/p\u003e\n\u003cp\u003eCyclopofol is a new sedative anesthetic independently developed in China, which has a low incidence of adverse reactions such as hypotension, bradycardia and respiratory depression [5]. At present, the commonly used dose is 0.4 mg/kg, which can be safely used for short operations such as painless gastroenteroscopy, bronchoscopy, and endoscopic retrograde cholangiopancreatography [6-7]. A number of studies have shown that cyclopofol can also be safely and effectively used for induction and maintenance of general anesthesia, and the dosage range is 0.4~0.9 mg/kg, and compared with propofol, cardiovascular adverse events are significantly reduced, and blood pressure and heart rate are less increased. Li et al. [8] studied the potential effects of dose and age on the pharmacokinetic characteristics and safety of cyclopofol, and believed that the dosage of 0.3 mg/kg of cyclopofol should be selected for clinical use in elderly patients. Elderly diabetic patients are sensitive to anesthetic drugs, have weak compensatory capacity, and are prone to cardiovascular and cerebrovascular accidents, so the dose and safety of the drug need to be further evaluated. The purpose of this study was to investigate the safety and effectiveness of different doses of cyclopofol in the induction of general anesthesia in elderly diabetic patients, and to provide reference for clinical work.\u003c/p\u003e"},{"header":"Data and methods","content":"\u003cp\u003e1.1 General Information\u003c/p\u003e\n\u003cp\u003eThe present prospective, double-blind, single-center study was conducted at The Second hospital of Shanxi Medical University Hospital. This study was approved by the Ethics Committee of the Second Hospital of Shanxi Medical University (review board number [2024] YX 021), and patients or their families signed informed consent. Select data and methods from 2024.2-2024.6. The trial was registered at Chinese ClinicalTrials.gov in 26/02/2024(Registration number:ChiCTR2400081164). Written informed consent was obtained from all participants. Tis manuscript adheres to the applicable EQUATOR guidelines.\u003c/p\u003e\n\u003cp\u003e1.1 General Information\u003c/p\u003e\n\u003cp\u003ePatients with spinal single-level PLIF operation who were hospitalized in the Second Clinical College of Shanxi Medical University from 2024.2-2024.6 and planned to undergo elective tracheal intubation under general anesthesia were selected as the study objects. According to the results of previous studies, we assumed that the significance level \u0026alpha; was 0.05 and the test efficacy 1-\u0026beta; was 0.9. The sample size was calculated to be 70 cases, and the sample size was increased to 90 cases considering the factors such as loss of follow-up. SPSS 26.0 software was used to generate random numbers, and the study subjects were randomly divided into 3 groups. The induced dose of cyclopofol was 0.2 mg/kg in group A, 0.3 mg/kg in group B, and 0.4 mg/kg in group C.\u003c/p\u003e\n\u003cp\u003e1.2 Inclusion criteria: (1) Diabetic patients (all of whom were clearly diagnosed by secondary and above public hospitals); (2) Age \u0026ge;65 years old; (3) ASA grade Ⅱ-Ⅲ; (4) BMI: 18-30 kg/m2 (5) Selected patients who received general anesthesia tracheal intubation lumbar PLIF (single level).\u003c/p\u003e\n\u003cp\u003e1.3 Exclusion criteria: cyclopofol allergy, abnormal liver and kidney function, bradycardia (heart rate \u0026lt; 60 beats/min), hypotension (mean arterial pressure \u0026lt; 55 mmhg), prolonged QT interval, could not cooperate with researchers. After assessing patient eligibility, \u0026nbsp; they were informed regarding the study by members \u0026nbsp; of the study team, with written informed consent then \u0026nbsp; being obtained.\u003c/p\u003e\n\u003cp\u003e1.4 Research Methods\u003c/p\u003e\n\u003cp\u003eAfter the patient was admitted, peripheral venous channels were opened and ECG monitoring was performed. HR, BP, ECG, SpO2, RR, BIS were monitored. Radial artery puncture catheters were placed under 2% lidocaine 2 ml local anesthesia, invasive arterial pressure was monitored, and blood glucose (T0) was measured. After the invasive arterial pressure monitoring operation was completed, nasal catheter oxygen was administered for 2 L/min, midazolam was given 0.02 mg/kg, and intravenous injection was given slowly. When the patient\u0026apos;s sedation score (Ramsay score) was 3, blood pressure and heart rate at this time were recorded as the basic blood pressure and basic heart rate.\u003c/p\u003e\n\u003cp\u003eOxygen was absorbed in the mask for 5 L/min, and after full pre-oxygenation, Sufentanil 0.4ug /kg and cyclopofol were given successively (0.2mg /kg in group A, 0.3mg /kg in group B and 0.4mg /kg in group C, all diluted to 20 ml by 0.9% sodium chloride solution) for 30s. After the patient\u0026apos;s eyelash reflex disappeared, rocuronium 0.7 mg/kg was injected, and the observation indicators were recorded. If BIS is still greater than 60 after 5 minutes of induction, propofol 0.5 mg/kg remedial therapy is given (and the case is excluded). Tracheal intubation was performed after successful induction (visual laryngoscope was used; successful intubation was required once; unsuccessful cases were excluded), and blood glucose (T1) was monitored 2min after intubation and intubation reaction was recorded. After intubation, a ventilator was connected for assisted ventilation. Respiratory parameters were set as follows: oxygen flow rate of 2 L/min, tidal volume of 6-8 ml/kg, respiratory rate of 10-14 times /min, suction/breath ratio of 1:2, and PetCO2 was maintained between 30-40 mmHg. Propofol 4-12 mg\u0026middot;kg-1\u0026middot;h-1 and reifentanil 8-15ug\u0026middot;kg-1\u0026middot;min-1 were selected for anesthesia maintenance, and the drug concentration was adjusted so that BIS fluctuated between 40-60. During the operation, the anesthesiologist added analgesia and muscle relaxants according to the patient\u0026apos;s conditions, such as hypotension and bradycardia. The anesthesiologist selects vasoactive drugs according to the patient\u0026apos;s condition. After the operation, after the patient became conscious, the cough reflex recovered, and breathing returned to normal (VT\u0026gt;6 mL/kg, respiratory rate \u0026gt;10 times /min, end-tidal CO2 (ETCO2) \u0026lt;45 mmHg), the tracheal catheter was removed and sent to PACU. All of the above procedures are performed by a professional anesthesiologist.\u003c/p\u003e\n\u003cp\u003e1.5 Observation Indicators\u003c/p\u003e\n\u003cp\u003e1.5.1 Main outcome measures: Incidence of hypotension at induction of anesthesia (mean arterial pressure \u0026lt; 55 mmhg and lasting for at least one minute).\u003c/p\u003e\n\u003cp\u003e1.5.2 Minor Observation Indicators: Area under the curve (AUCMAP) of blood pressure below BBP during anesthesia induction, incidence of bradycardia (heart rate \u0026lt; 50 beats/min), area under the curve of heart rate below BHR (AUCHR), time to disappearance of eyelash reflexia, time for BIS to drop to 60, intubation response (within 3 minutes after intubation, Systolic blood pressure, diastolic blood pressure, or heart rate \u0026gt; 20% of the baseline value), the number of intraoperative hypotension episodes, the number of vasoactive drugs used, the dosage of pressors, and the blood glucose levels at 2 minutes after entry and intubation.\u003c/p\u003e\n\u003cp\u003e1.6 Statistical Methods\u003c/p\u003e\n\u003cp\u003eSPSS 26.0 software was used for statistical analysis. The measurement data of normal distribution were expressed as mean \u0026plusmn; standard deviation (), and ANOVA was used for inter-group comparison. The measurement data of the non-normal distribution were expressed as the median (interquartile distance), and the multiple local rank sum test was used for inter-group comparison. The count data were expressed as rate (%), and the Chi-square test or Fisher exact probability method were used for comparison between groups. P \u0026lt; 0.05 was considered statistically significant. Patients with spinal single-level PLIF who were admitted to the Second Clinical College of Shanxi Medical University and planned to undergo elective tracheal intubation under general anesthesia were studied. According to the results of previous studies, we assumed that the significance level \u0026alpha; was 0.05 and the test efficacy 1-\u0026beta; was 0.9. The sample size was calculated to be 70 cases, and the sample size was increased to 90 cases considering the factors such as loss of follow-up. SPSS 26.0 software was used to generate random numbers, and the study subjects were randomly divided into 3 groups. The induced dose of cyclopofol was 0.2 mg/kg in group A, 0.3 mg/kg in group B, and 0.4 mg/kg in group C.\u003c/p\u003e\n\u003cp\u003e1.2 Inclusion criteria: (1) Diabetic patients (all of whom were clearly diagnosed by secondary and above public hospitals); (2) Age \u0026ge;65 years old; (3) ASA grade Ⅱ-Ⅲ; (4) BMI: 18-30 kg/m2 (5) Selected patients who received general anesthesia tracheal intubation lumbar PLIF (single level).\u003c/p\u003e\n\u003cp\u003e1.3 Exclusion criteria: cyclopofol allergy, abnormal liver and kidney function, bradycardia (heart rate \u0026lt; 60 beats/min), hypotension (mean arterial pressure \u0026lt; 55 mmhg), prolonged QT interval, could not cooperate with researchers.\u003c/p\u003e\n\u003cp\u003e1.4 Research Methods\u003c/p\u003e\n\u003cp\u003eAfter the patient was admitted, peripheral venous channels were opened and ECG monitoring was performed. HR, BP, ECG, SpO2, RR, BIS were monitored. Radial artery puncture catheters were placed under 2% lidocaine 2 ml local anesthesia, invasive arterial pressure was monitored, and blood glucose (T0) was measured. After the invasive arterial pressure monitoring operation was completed, nasal catheter oxygen was administered for 2 L/min, midazolam was given 0.02 mg/kg, and intravenous injection was given slowly. When the patient\u0026apos;s sedation score (Ramsay score) was 3, blood pressure and heart rate at this time were recorded as the basic blood pressure and basic heart rate.\u003c/p\u003e\n\u003cp\u003eOxygen was absorbed in the mask for 5 L/min, and after full pre-oxygenation, Sufentanil 0.4ug /kg and cyclopofol were given successively (0.2mg /kg in group A, 0.3mg /kg in group B and 0.4mg /kg in group C, all diluted to 20 ml by 0.9% sodium chloride solution) for 30s. After the patient\u0026apos;s eyelash reflex disappeared, rocuronium 0.7 mg/kg was injected, and the observation indicators were recorded. If BIS is still greater than 60 after 5 minutes of induction, propofol 0.5 mg/kg remedial therapy is given (and the case is excluded). Tracheal intubation was performed after successful induction (visual laryngoscope was used; successful intubation was required once; unsuccessful cases were excluded), and blood glucose (T1) was monitored 2min after intubation and intubation reaction was recorded. After intubation, a ventilator was connected for assisted ventilation. Respiratory parameters were set as follows: oxygen flow rate of 2 L/min, tidal volume of 6-8 ml/kg, respiratory rate of 10-14 times /min, suction/breath ratio of 1:2, and PetCO2 was maintained between 30-40 mmHg. Propofol 4-12 mg\u0026middot;kg-1\u0026middot;h-1 and reifentanil 8-15ug\u0026middot;kg-1\u0026middot;min-1 were selected for anesthesia maintenance, and the drug concentration was adjusted so that BIS fluctuated between 40-60. During the operation, the anesthesiologist added analgesia and muscle relaxants according to the patient\u0026apos;s conditions, such as hypotension and bradycardia. The anesthesiologist selects vasoactive drugs according to the patient\u0026apos;s condition. After the operation, after the patient became conscious, the cough reflex recovered, and breathing returned to normal (VT\u0026gt;6 mL/kg, respiratory rate \u0026gt;10 times /min, end-tidal CO2 (ETCO2) \u0026lt;45 mmHg), the tracheal catheter was removed and sent to PACU. All of the above procedures are performed by a professional anesthesiologist.\u003c/p\u003e\n\u003cp\u003e1.5 Observation Indicators\u003c/p\u003e\n\u003cp\u003e1.5.1 Main outcome measures: Incidence of hypotension at induction of anesthesia (mean arterial pressure \u0026lt; 55 mmhg and lasting for at least one minute).\u003c/p\u003e\n\u003cp\u003e1.5.2 Minor Observation Indicators: Area under the curve (AUCMAP) of blood pressure below BBP during anesthesia induction, incidence of bradycardia (heart rate \u0026lt; 50 beats/min), area under the curve of heart rate below BHR (AUCHR), time to disappearance of eyelash reflexia, time for BIS to drop to 60, intubation response (within 3 minutes after intubation, Systolic blood pressure, diastolic blood pressure, or heart rate \u0026gt; 20% of the baseline value), the number of intraoperative hypotension episodes, the number of vasoactive drugs used, the dosage of pressors, and the blood glucose levels at 2 minutes after entry and intubation.\u003c/p\u003e\n\u003cp\u003e1.6 Statistical Methods\u003c/p\u003e\n\u003cp\u003eSPSS 26.0 software was used for statistical analysis. The measurement data of normal distribution were expressed as mean \u0026plusmn; standard deviation (), and ANOVA was used for inter-group comparison. The measurement data of the non-normal distribution were expressed as the median (interquartile distance), and the multiple local rank sum test was used for inter-group comparison. The count data were expressed as rate (%), and the Chi-square test or Fisher exact probability method were used for comparison between groups. P \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e2.1 Comparison of general conditions of patients in the three groups A total of 90 patients were included in this study, among which 6 patients were excluded due to unsuccessful first intubation, 2 patients were excluded due to the need for propofol remediation, and the remaining 82 patients completed the study, as shown in Figure 1. There was no statistical significance in the comparison of general data among the three groups (P\u0026lt;0.05), as shown in Table 1.\u003c/p\u003e\n\u003cp\u003e2.2 Hemodynamic comparison among the three groups, the incidence of hypotension in group C was the highest, and the difference was statistically significant compared with group A and Group B. Although group B was higher than group A, the difference was not statistically significant. AUCMAP showed that group C was higher than group B and group B was higher than group A, and the difference was statistically significant. The incidence of bradycardia in group C was the highest, and the difference was statistically significant compared with group A. Compared with the three groups, the AUCHR of group C was greater than that of group B and that of group A, but only the difference between group A and group C was statistically significant. The incidence of intubation reaction in group A was the highest, and the difference was statistically significant compared with the other two groups (see Table 2).\u003c/p\u003e\n\u003cp\u003e2.3 The sedation effect of patients in the three groups was compared with the disappearance time of eyelash reflex, the time required for BIS to drop to 60, the blood sugar value at two time points, and the frequency of intraoperative hypotension. There were no statistically significant differences among the three groups (see Table 2). However, the lowest BIS value was found in group C, which showed A statistically significant difference compared with group A and B. The change trend of BIS showed that the BIS reached the lowest value in about 1 minute and then rose slowly. Although the BIS values were all less than 60, the BIS values in group A were higher than those in group B and group C at the 3rd, 4th and 5th minute, and the difference was statistically significant.\u003c/p\u003e\n\u003cp\u003eTable 1 Comparison of general conditions among the three groups\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.6479%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.3099%;\"\u003e\n \u003cp\u003eGroup A\u003c/p\u003e\n \u003cp\u003e（n=27）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.4859%;\"\u003e\n \u003cp\u003eGroup B\u003c/p\u003e\n \u003cp\u003e（n=27）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.838%;\"\u003e\n \u003cp\u003eGroup C\u003c/p\u003e\n \u003cp\u003e（n=28）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.3873%;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.33099%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.6479%;\"\u003e\n \u003cp\u003eGender (Male)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.3099%;\"\u003e\n \u003cp\u003e14（27）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.4859%;\"\u003e\n \u003cp\u003e16（27）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.838%;\"\u003e\n \u003cp\u003e14（28）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.3873%;\"\u003e\n \u003cp\u003e0.768\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.33099%;\"\u003e\n \u003cp\u003e0.527\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.6479%;\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.3099%;\"\u003e\n \u003cp\u003e71.33\u0026plusmn;4.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.4859%;\"\u003e\n \u003cp\u003e69.59\u0026plusmn;3.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.838%;\"\u003e\n \u003cp\u003e71.96\u0026plusmn;3.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.3873%;\"\u003e\n \u003cp\u003e0.076\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.33099%;\"\u003e\n \u003cp\u003e2.658\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.6479%;\"\u003e\n \u003cp\u003eBMI（km/m\u003csup\u003e2\u003c/sup\u003e）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.3099%;\"\u003e\n \u003cp\u003e22.72（2.66）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.4859%;\"\u003e\n \u003cp\u003e22.68（2.41）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.838%;\"\u003e\n \u003cp\u003e23.29（1.66）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.3873%;\"\u003e\n \u003cp\u003e0.575\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.33099%;\"\u003e\n \u003cp\u003e1.106\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.6479%;\"\u003e\n \u003cp\u003eASA（Ⅱ）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.3099%;\"\u003e\n \u003cp\u003e13（27）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.4859%;\"\u003e\n \u003cp\u003e17（27）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.838%;\"\u003e\n \u003cp\u003e14（28）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.3873%;\"\u003e\n \u003cp\u003e0.492\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.33099%;\"\u003e\n \u003cp\u003e1.420\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.6479%;\"\u003e\n \u003cp\u003eDuration of diabetes\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.3099%;\"\u003e\n \u003cp\u003e6.00（8.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.4859%;\"\u003e\n \u003cp\u003e7.00（8.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.838%;\"\u003e\n \u003cp\u003e6.50（10.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.3873%;\"\u003e\n \u003cp\u003e0.931\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.33099%;\"\u003e\n \u003cp\u003e0.143\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.6479%;\"\u003e\n \u003cp\u003eCombined hypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.3099%;\"\u003e\n \u003cp\u003e18（27）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.4859%;\"\u003e\n \u003cp\u003e13（27）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.838%;\"\u003e\n \u003cp\u003e16（28）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.3873%;\"\u003e\n \u003cp\u003e0.370\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.33099%;\"\u003e\n \u003cp\u003e1.990\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.6479%;\"\u003e\n \u003cp\u003eComplicated with coronary heart disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.3099%;\"\u003e\n \u003cp\u003e12（27）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.4859%;\"\u003e\n \u003cp\u003e12（27）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.838%;\"\u003e\n \u003cp\u003e8（28）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.3873%;\"\u003e\n \u003cp\u003e0.377\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.33099%;\"\u003e\n \u003cp\u003e1.952\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.6479%;\"\u003e\n \u003cp\u003eBasal mean arterial pressure(mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.3099%;\"\u003e\n \u003cp\u003e98.37\u0026plusmn;4.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.4859%;\"\u003e\n \u003cp\u003e97.63\u0026plusmn;4.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.838%;\"\u003e\n \u003cp\u003e99.64\u0026plusmn;6.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.3873%;\"\u003e\n \u003cp\u003e0.396\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.33099%;\"\u003e\n \u003cp\u003e0.937\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.6479%;\"\u003e\n \u003cp\u003eBasal heart rate (times/min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.3099%;\"\u003e\n \u003cp\u003e68.93\u0026plusmn;4.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.4859%;\"\u003e\n \u003cp\u003e71.67\u0026plusmn;5.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.838%;\"\u003e\n \u003cp\u003e72.29\u0026plusmn;5.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.3873%;\"\u003e\n \u003cp\u003e0.051\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.33099%;\"\u003e\n \u003cp\u003e3.092\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.6479%;\"\u003e\n \u003cp\u003eBlood sugar levels at the time of entry\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.3099%;\"\u003e\n \u003cp\u003e6.34\u0026plusmn;0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.4859%;\"\u003e\n \u003cp\u003e6.06\u0026plusmn;0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.838%;\"\u003e\n \u003cp\u003e6.15\u0026plusmn;0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.3873%;\"\u003e\n \u003cp\u003e0.320\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.33099%;\"\u003e\n \u003cp\u003e1.155\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.6479%;\"\u003e\n \u003cp\u003eOperation duration（min）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.3099%;\"\u003e\n \u003cp\u003e138.78\u0026plusmn;13.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.4859%;\"\u003e\n \u003cp\u003e139.37\u0026plusmn;17.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.838%;\"\u003e\n \u003cp\u003e143.32\u0026plusmn;17.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.3873%;\"\u003e\n \u003cp\u003e0.524\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.33099%;\"\u003e\n \u003cp\u003e0.652\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.6479%;\"\u003e\n \u003cp\u003eAnesthesia duration （min）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.3099%;\"\u003e\n \u003cp\u003e188.96\u0026plusmn;14.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.4859%;\"\u003e\n \u003cp\u003e186.78\u0026plusmn;13.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.838%;\"\u003e\n \u003cp\u003e188.32\u0026plusmn;16.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.3873%;\"\u003e\n \u003cp\u003e0.861\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.33099%;\"\u003e\n \u003cp\u003e0.150\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.6479%;\"\u003e\n \u003cp\u003eLiquid intake（ml）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.3099%;\"\u003e\n \u003cp\u003e1600（500）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.4859%;\"\u003e\n \u003cp\u003e1750（500）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.838%;\"\u003e\n \u003cp\u003e1750（500）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.3873%;\"\u003e\n \u003cp\u003e0.764\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.33099%;\"\u003e\n \u003cp\u003e0.538\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.6479%;\"\u003e\n \u003cp\u003eAmount of bleeding（ml）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.3099%;\"\u003e\n \u003cp\u003e190（40）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.4859%;\"\u003e\n \u003cp\u003e210（60）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.838%;\"\u003e\n \u003cp\u003e190（50）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.3873%;\"\u003e\n \u003cp\u003e0.921\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.33099%;\"\u003e\n \u003cp\u003e0.165\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eTable 2 Comparison of induction conditions among the three groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 22.8471%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.8594%;\"\u003e\n \u003cp\u003eGroup A\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2777%;\"\u003e\n \u003cp\u003eGroup B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.2109%;\"\u003e\n \u003cp\u003eGroup C\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.96309%;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.84183%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 22.8471%;\"\u003e\n \u003cp\u003eHypotension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.8594%;\"\u003e\n \u003cp\u003e2（7.4%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2777%;\"\u003e\n \u003cp\u003e4（14.8%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.2109%;\"\u003e\n \u003cp\u003e14\u003csup\u003eab\u003c/sup\u003e（46.4%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.96309%;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.84183%;\"\u003e\n \u003cp\u003e13.336\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 22.8471%;\"\u003e\n \u003cp\u003eAUC\u003csub\u003eMAP\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.8594%;\"\u003e\n \u003cp\u003e143.59\u0026plusmn;19.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2777%;\"\u003e\n \u003cp\u003e158.44\u0026plusmn;26.55\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.2109%;\"\u003e\n \u003cp\u003e176.39\u0026plusmn;33.83\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.96309%;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.84183%;\"\u003e\n \u003cp\u003e10.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 22.8471%;\"\u003e\n \u003cp\u003eBradycardia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.8594%;\"\u003e\n \u003cp\u003e5（18.5%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2777%;\"\u003e\n \u003cp\u003e8（29.6%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.2109%;\"\u003e\n \u003cp\u003e15\u003csup\u003ea\u003c/sup\u003e（53.6%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.96309%;\"\u003e\n \u003cp\u003e0.019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.84183%;\"\u003e\n \u003cp\u003e7.876\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 22.8471%;\"\u003e\n \u003cp\u003eAUC\u003csub\u003eHR\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.8594%;\"\u003e\n \u003cp\u003e63.52\u0026plusmn;19.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2777%;\"\u003e\n \u003cp\u003e80.26\u0026plusmn;25.97\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.2109%;\"\u003e\n \u003cp\u003e96.25\u0026plusmn;26.54\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.96309%;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.84183%;\"\u003e\n \u003cp\u003e12.60\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 22.8471%;\"\u003e\n \u003cp\u003eAUC\u003csub\u003eBIS\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.8594%;\"\u003e\n \u003cp\u003e191.15\u0026plusmn;11.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2777%;\"\u003e\n \u003cp\u003e204.67\u0026plusmn;10.40\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.2109%;\"\u003e\n \u003cp\u003e208.43\u0026plusmn;12.60\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.96309%;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.84183%;\"\u003e\n \u003cp\u003e17.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 22.8471%;\"\u003e\n \u003cp\u003eIntubation reaction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.8594%;\"\u003e\n \u003cp\u003e21（77.8%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2777%;\"\u003e\n \u003cp\u003e4（14.8%）\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.2109%;\"\u003e\n \u003cp\u003e2（7.1%）\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.96309%;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.84183%;\"\u003e\n \u003cp\u003e37.032\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 22.8471%;\"\u003e\n \u003cp\u003eEyelash reflexes disappear time\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.8594%;\"\u003e\n \u003cp\u003e57.85\u0026plusmn;7.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2777%;\"\u003e\n \u003cp\u003e56.70\u0026plusmn;6.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.2109%;\"\u003e\n \u003cp\u003e57.25\u0026plusmn;10.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.96309%;\"\u003e\n \u003cp\u003e0.839\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.84183%;\"\u003e\n \u003cp\u003e0.176\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 22.8471%;\"\u003e\n \u003cp\u003eTime for BIS drop to 60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.8594%;\"\u003e\n \u003cp\u003e66.59\u0026plusmn;8.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2777%;\"\u003e\n \u003cp\u003e67.07\u0026plusmn;7.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.2109%;\"\u003e\n \u003cp\u003e68.11\u0026plusmn;9.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.96309%;\"\u003e\n \u003cp\u003e0.790\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.84183%;\"\u003e\n \u003cp\u003e33.049\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 22.8471%;\"\u003e\n \u003cp\u003eBlood sugar levels after intubation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.8594%;\"\u003e\n \u003cp\u003e8.03\u0026plusmn;0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2777%;\"\u003e\n \u003cp\u003e7.88\u0026plusmn;0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.2109%;\"\u003e\n \u003cp\u003e7.82\u0026plusmn;0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.96309%;\"\u003e\n \u003cp\u003e0.322\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.84183%;\"\u003e\n \u003cp\u003e1.150\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: Compared with group A, aP\u0026lt;0.05, compared with group B, bP\u0026lt;0.05\u003c/p\u003e\n\u003cp\u003eTable 3 Comparison of intraoperative hypotension among the three groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47.8873%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6197%;\"\u003e\n \u003cp\u003eA组\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.5493%;\"\u003e\n \u003cp\u003eB组\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9648%;\"\u003e\n \u003cp\u003eC组\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.97887%;\"\u003e\n \u003cp\u003eP值\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47.8873%;\"\u003e\n \u003cp\u003eFrequency of intraoperative hypotension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6197%;\"\u003e\n \u003cp\u003e5（2）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.5493%;\"\u003e\n \u003cp\u003e5（1）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9648%;\"\u003e\n \u003cp\u003e4（2）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.97887%;\"\u003e\n \u003cp\u003e0.778\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47.8873%;\"\u003e\n \u003cp\u003ePressors were used during the operation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6197%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.5493%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9648%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.97887%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47.8873%;\"\u003e\n \u003cp\u003eephedrine（mg）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6197%;\"\u003e\n \u003cp\u003e18（6）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.5493%;\"\u003e\n \u003cp\u003e18（6）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9648%;\"\u003e\n \u003cp\u003e12（6）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.97887%;\"\u003e\n \u003cp\u003e0.228\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47.8873%;\"\u003e\n \u003cp\u003edopamine（mg）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6197%;\"\u003e\n \u003cp\u003e3（4）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.5493%;\"\u003e\n \u003cp\u003e2.5（3.75）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9648%;\"\u003e\n \u003cp\u003e5（3.75）\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.97887%;\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: Compared with group A, aP\u0026lt;0.05, compared with group B, bP\u0026lt;0.05\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study compared the effects of different doses of cyclopofol on hemodynamics and anesthetic effects of total intoxication induction in elderly diabetic patients. The type of surgery selected was single-stage spinal PILF surgery, because this surgery is a programmed surgery with relatively fixed operation time and blood loss, which can reduce the influence of surgery on hemodynamics.\u003c/p\u003e\n\u003cp\u003eThis study found that 0.4 mg/kg cyclopofol combined with 0.4 ug/kg sufentanil and 0.7 mg/kg rocuronium had a higher incidence of hypotension during induction than 0.3 mg/kg and 0.2 mg/kg groups, and the difference was statistically significant. Previous studies [9] also found that 0.4mg /kg cyclopofol induced hypotension had a high probability (57%), which was higher than 46.4% in this study. This may be because hypotension was defined in this study as MAP \u0026lt; 60 mmHg or 30% of the basic blood pressure, while the definition of hypotension in this study was MAP \u0026lt; 55 mmHg. Last 1 minute. Two retrospective studies [10-11] found that intraoperative MAP less than 55 mmHg was associated with AKI and myocardial damage even if the duration was shorter, so hypotension was defined in this study as MAP less than 55 mmHg lasting 1 minute. The use of the subthreshold area method [12], while taking into account the duration and severity of the blood pressure drop, can more fully reflect the situation of blood pressure at induction, and thus better assess the harm of hypotension. Therefore, this study compared the area of MAP lower than the basic value during induction among all groups, and found that the 0.4 mg/kg group was higher than the 0.3 mg/kg and 0.2 mg/kg groups, and the 0.3 mg/kg group was higher than the 0.2 mg/kg group, and the difference was statistically significant. Although there was no statistically significant difference in the incidence of hypotension between the 0.3 and 0.2 groups, AUCMAP in the 0.2 mg group was significantly lower than that in the 0.3 mg group, indicating that the effect of induction on blood pressure in the 0.2 mg group was lower. This study described that the change of heart rate in each group was consistent with the change of blood pressure, indicating that induction in the 0.2 mg/kg group had the least effect on blood pressure and heart rate.\u003c/p\u003e\n\u003cp\u003eThis study also found that although there was no statistical significance in the disappearance time of eyelash reflex and the reduction time of BIS below 60 in the 0.2 mg group compared with the other two groups, and the BIS was always lower than 60, the intubation response of the 0.2 mg/kg group was significantly higher than that of the other two groups. At the same time, this study found that the area under the curve of BIS in group A was lower than that in groups B and C, and the BIS value at 3, 4 and 5 minutes after induction in group A was higher than that in the other two groups. However, hypertension and tachycardia caused by intubation response are risk factors for myocardial infarction and stroke [13-14], which is a particular concern for elderly patients and patients with a history of myocardial infarction or stroke [15-17]. Therefore, it is very important to prevent hemodynamic fluctuations of tracheal intubation. Therefore, although previous studies believed that 0.2 mg/kg cyclopofol could meet the demand for sedation during induction, which was consistent with the results of this study, this study found that this group had a high incidence of intubation reaction and was not suitable for elderly diabetic patients.\u003c/p\u003e\n\u003cp\u003eThe blood glucose of the three groups was the highest in group A at 2 minutes after intubation, but the difference was not statistically significant. The reason for the increase of blood glucose in group A may be related to the intubation response, and the difference was not statistically significant at present, which may be related to the sample size. There was no statistically significant difference in the number of intraoperative hypotension occurrence and ephedrine dosage among the three groups, but the 0.4mg dopamine dosage group was significantly higher than the other two groups (Table 3), which may be related to the medication habits of researchers. Ephedrine is usually used to treat hypotension. When ephedrine is not effective for a single treatment, dopamine will continue to be injected. Therefore, the failure to observe more intraoperative hypotension in patients in the 0.4 mg group may be related to the pumping of dopamine, which can also indicate that the 0.4 mg group has a greater impact on intraoperative blood pressure.\u003c/p\u003e\n\u003cp\u003eThis trial was a single-center trial with a small sample size, and the clinical outcome indicators (such as the incidence of postoperative cardiovascular events and cerebrovascular events, etc.) of the three groups of patients were not observed. After that, a large-sample multi-center clinical trial is needed to reach a more comprehensive conclusion.\u003c/p\u003e\n\u003cp\u003eIn summary, 0.3 mg/kg cypofol in the induction period of elderly diabetic patients has more stable circulation and less vasoactive drug dosage during induction, which is better than 0.2 and 0.4 mg/kg dosage groups.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo;s Contribution\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Jiang Xiaorui: Design paper, draft paper, write paper; Zhang Linzhong: experimental design, paper modification; Jiang Xiaorui, JI Jiawei, Jing Yan: Research process implementation and data collection; Li Meiping: Data analysis. All authors read and approved the final manuscript and agreed to publish it.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all the reviewers who participated in the review and MJEditor (www. mjedi tor. com) for its linguistic assistance during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the grants from Department of Science and Technology of Shanxi Province \u0026nbsp;(Grant ID:201701D121139) and Beijing Health Alliance Charitable Foundation(grant ID: YXHA-ARP-006).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the fndings of this study are available from the corresponding author, Lin-zhong Zhang, upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that there is no conflict of interest\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGilbert T, Neuburger J, Kraindler J, et al. 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J Physiol. 1969;200:25\u0026ndash;49. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1113/jphysiol.1969.sp008680\u003c/span\u003e\u003cspan address=\"10.1113/jphysiol.1969.sp008680\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Older adults, Diabetes mellitus, ciprofol, General anesthesia induction","lastPublishedDoi":"10.21203/rs.3.rs-5089178/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5089178/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eObjective \u0026nbsp;To investigate the safety and efficacy of different doses ciprofol in induction of general anesthesia in elderly diabetic patients. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMethods \u0026nbsp;Ninety spinal single-level PLIF patients who were planned to undergo elective tracheal intubation under general anesthesia were selected as the subjects.The study subjects were randomly divided into 3 groups. Ciprofol induction dose was 0.2 mg/kg in group A, 0.3 mg/kg in group B and 0.4 mg/kg in group C, The safety and efficacy of general anesthesia induction were compared among the three groups. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eResults \u0026nbsp;The incidence of hypotension in group C (46.4%) was significantly higher than that in group A (7.4%) and group B (14.8%) (P \u0026lt; 0.05). AUCMAP of the three groups was higher in group C (176.39±33.83 mmHg.min) than in group B (158.44±26.55 mmHg.min) and higher in group B than in group A (143.59±19.52 mmHg.min), P \u0026lt; 0.05. The incidence of intubation reaction in group A (77.8%) was the highest (P \u0026lt; 0.05). There were significant differences in BIS values at 3, 4 and 5 minutes after administration.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConclusion \u0026nbsp;The use of 0.3mg/kg ciprofol in the induction period in elderly diabetic patients has more stable circulation and less vasoactive drug dosage during induction, which is better than 0.2 and 0.4mg/kg dosage groups. The trial was registered at Chinese ClinicalTrials.gov in February 26, 2024 (Registration number:ChiCTR2400081164).\u003c/p\u003e","manuscriptTitle":"Effect of Different Doses of Ciprofol on Hemodynamics Induced By General Anesthesia in Elderly Diabetic Patients Undergoing Spinal Surgery: A double-blind, randomized, controlled study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-16 09:54:37","doi":"10.21203/rs.3.rs-5089178/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-26T18:58:43+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-09-24T11:28:42+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-09-24T11:23:54+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Anesthesiology","date":"2024-09-14T12:39:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dc1a681f-470c-49eb-a0cc-7daa544e0f58","owner":[],"postedDate":"December 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-01-27T16:00:46+00:00","versionOfRecord":{"articleIdentity":"rs-5089178","link":"https://doi.org/10.1186/s12871-024-02881-3","journal":{"identity":"bmc-anesthesiology","isVorOnly":false,"title":"BMC Anesthesiology"},"publishedOn":"2025-01-20 15:57:22","publishedOnDateReadable":"January 20th, 2025"},"versionCreatedAt":"2024-12-16 09:54:37","video":"","vorDoi":"10.1186/s12871-024-02881-3","vorDoiUrl":"https://doi.org/10.1186/s12871-024-02881-3","workflowStages":[]},"version":"v1","identity":"rs-5089178","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5089178","identity":"rs-5089178","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}