A Comparison of the Effect of Sevoflurane and Propofol on Ventricular Repolarisation After Preoperative Cefuroxime Infusion

Hindawi BioMed Research International Volume 2019, Article ID 8978906, 6 pages https://doi.org/10.1155/2019/8978906

Research Article A Comparison of the Effect of Sevoflurane and Propofol on Ventricular Repolarisation after Preoperative Cefuroxime Infusion

Yanqiu Liu,1 Hong Gao ,1 Guilong Wang ,2 Li An,1 Jing Yi,2 Xiaokui Fu,2 Chunlei Wen,2 and Zijun Wang2

1 Department of Anesthesiology, Te Afliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China 2Department of Anesthesiology, Guizhou Medical University, Guiyang, Guizhou, China

Correspondence should be addressed to Hong Gao; [email protected]

Received 10 July 2018; Revised 11 December 2018; Accepted 13 December 2018; Published 2 January 2019

Academic Editor: Gianluca Di Bella

Copyright © 2019 Yanqiu Liu et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Te aim of this study is to investigate the changes in QT, QTc, and Tp-e intervals and Tp-e/QT ratio on surface electrocardiogram (ECG) signals during anaesthesia induction using propofol or sevofurane afer preoperative cefuroxime infusion. Some 120 cases of gynaecological patients are randomly divided into propofol (P) and sevofurane (S) groups (n=60). Afer cefuroxime (1.5 g) was infused in the two groups of patients, propofol target controlled infusion (TCI) was conducted in the P group for 5 min to realise a plasma concentration of 4 �g/ml while patients in the S group inhaled anaesthesia by infusing 1.3 MAC sevofurane for 6 min. Te 12-lead ECGs were separately collected before infusing cefuroxime (T1), afer infusing cefuroxime (T2), and afer infusing propofol or sevofurane (T3) to measure QT and Tp-e intervals, calculate QTc and Tp-e/QT, and record MAP and HR. Finally, we demonstrated that QT, QTc, and Tp-e intervals and Tp-e/QT ratio had no change (P > 0.05) afer cefuroxime infusion in the two groups of patients compared with that before infusing antibiotics. Moreover, afer conducting preoperative cefuroxime infusion, using propofol and sevofurane had no infuence on Tp-e interval, but sevofurane can signifcantly prolong QT and QTc intervals (P < 0.05).

1. Introduction sevofurane (inhalation anaesthetic) prolongs the QT interval [14]. Antibiotics and anaesthetics both have efects on QT Antibioticsarethefavouritedrugsusedtopreventandcure interval.Ithasnotbeenclarifedwhetherusingpropo- infectious diseases; however, the cardiotoxicity caused by fol or sevofurane, afer antibiotic infusion, will aggravate antibiotics cannot be ignored with the extending application abnormal ventricular repolarisation and increase TDR so in clinical practice [1–3]. It is reported that antibiotics as to increase perioperative arrhythmia. Te Tp-e interval, can prolong QT and QTc intervals [4–6]. Prolongation of the period from the peak-to-the end of the T-wave, is the QT interval increases transmural dispersion of repo- a remarkable refection of TDR in ECG and can fexibly larisation (TDR) of the ventricle, probably increasing the predict risk of arrhythmogenesis. In contrast, the ratio of risk of arrhythmia risk [5]. A case report indicates that Tp-e/QT excludes the infuence of HR [14–16]. Te study antibiotics can lead to torsade de pointes [7]. Generally, investigated the changes of QT, QTc, and Tp-e intervals and cephalosporin antibiotics are infused in surgical patients the ratio of Tp-e/QT in ECG during anaesthesia induction preoperatively to prevent postoperative wound infection by using propofol or sevofurane afer infusing cefuroxime. [8, 9]. In intraoperative periods, anaesthetic drugs also By doing so, the study evaluated the safety of patients afer infuence QT and QTc intervals [10–14]. Moreover, propo- being anaesthetised using propofol or sevofurane in view fol (intravenous anaesthetic) probably shortens, prolongs, of cardiac electrophysiology, which provides references for or does not change the QTc interval [10–12, 14] while future clinical anaesthesia. 2 BioMed Research International

2. Methods anaesthetic (assisted ventilation if necessary). During the period, SpO2 and PETCO2 were maintained at 99% to 100% Te experiment has been reviewed and approved by Medi- and 35 to 40 mmHg, respectively. cal Ethics Committee in the college (Application Number: Te QT, QTc, and Tp-e intervals and the ratio of Tp- 20150124, Guizhou Medical University), and the subjects have e/QT of the two groups of patients before infusing antibiotics given informed consent prior to participating in the study. (T1), afer infusing antibiotics (T2), and afer propofol TCI or sevofurane inhalation for specifc time (T3) were separately 2.1. Study Populations and Design. Tere were 120 cases of measured. Moreover, MAR and HR at T1 to T3 were recorded. elective gynaecological laparoscopic operation (hysteromy- omectomy, excision of ovarian cyst, and excision of ovarian 2.3. Electrocardiographic Measurements. Te ECG data were tumors) during January to November 2016 and patients aged analysed according to uniform standards afer completing from 20 to 50 showed ASA I or II. Te patients were found to the observation. According to literature [18] the V4 lead have normal preoperative cardiopulmonary function, ECG, was selected to measure the QT and Tp-e intervals. Te QT and electrolyte state, and the HR-corrected QT (QTc) interval interval was measured from the Q-wave start to the T-wave was less than 440 ms. Tey did not take medication for end while the Tp-e interval was measured from the peak-to- prolonging the QT interval including antiarrhythmic drugs, the end of the T-wave. Here, the peak of T wave refers to the blocking agent for � receptors, antidepressants, or phenoth- peak point of the T-wave and the terminal point of the T-wave iazine drugs. Moreover, they did not have diabetes or other represents the intersection point between the declined branch endocrine diseases. Te patients were randomly divided into tangent of the T-wave and the base line. If a U-wave appears, propofol (P) and sevofurane (S) groups using a random theterminalpointoftheT-waveistheincisurabetweentheT- number table, with 60 cases in each group. andU-waves[14].Treecontinuous,completeQTandTp-e intervalsweremeasuredbyusingtheV4leadtocalculatethe average value [13, 19]. According to the Bazett formula (QTc = 2.2. Procedure. Preoperative fasting and water-deprivation √�� of patients separately last for 8 h and 4 h and no patient QT/ ), the QTc and the ratio of Tp-e/QT were calculated [10]. took any preoperative medication. To prevent the infuence of diurnal change on QT interval, all of the experimental data were collected in the morning (8:30 to 11:30 A.M.) [17]. 2.4. Statistical Analysis. Statistical analysis was conducted Afer entering the operating room, the routine monitoring of byusingSPSS19.0sofware.Temeasurementdataare (�± ) MAP,HR, and SpO2 of patients was conducted. Afer opening represented by using mean and standard deviation s . the upper extremity vein (UEV), 130/0.4 sodium chloride Comparisons within group were conducted through repeated measures analysis of variance and a t-test was employed for injection (10 mL/kg) of hydroxyethyl starch (specifcation: < 500 mL/bag, batch number: 81KC081, Beijing Fresenius Kabi comparison between groups: P 0.05 denotes a statistically Medical Group) was infused to the UEV within 30 min. signifcant diference. Te ECG electrode was established and the frst ECG was obtained by using the ECG-1250C 12-lead electrocardio- 3. Results graph (Shanghai Photoelectric Medical Instrument Corpo- ration) at a chart speed of 25 mm/s and gain amplifcation (1) By comparing the two groups of patients under general of 10 mm/mV. Aferwards, cefuroxime sodium (antibiotic) conditions, it can be seen that diference is not statistically (1.5 g: batch number: 505316, specifcation: 0.75 g each, Esseti signifcant (P > 0.05), as shown in Table 1. Farmaceutici Srl, Italy) was put into 100 mL normal saline (2) By comparing the MAP and HR of the two groups and then intravenously infused within 20 min to collect the of patients at diferent time points, the diference was not second ECG. Next, the propofol (diprivan, 10 mg/mL, batch statistically signifcant (P > 0.05), as shown in Table 2. number: LC699; Corden Pharma S.P.A., Italy) TCI (Graseby (3) Te comparison of QT, QTc, and Tp-e intervals and Anaesthesia Pump 3500, UK) was applied to patients in the ratio of Tp-e/QT of the two groups of patients at diferent the P group. Te third ECG was collected afer the plasma times is summarised in Table 3. Te QT, QTc, and Tp-e concentrationreachedthetargetedlevelof4�g/mL and intervals and the ratio of Tp-e/QT of the two groups of was sustained for 5 min. Inhalation induction was conducted patients at T1 and T2 were compared and the diference was > to anaesthetise patients in the S group using sevofurane insignifcant (P 0.05). Compared with T1 and T2,theQT (batch number: 64181, specifcation: 250 mL/bottle, Maruishi and QTc intervals of the S group were prolonged at T3 (P Pharmaceutical Co., Ltd, Japan). Before induction, 8%v/v < 0.05) while the ratio of Tp-e/QT decreased (P < 0.05). of sevofurane and oxygen fow at 6 L/min was applied Compared with the P group, the QT and QTc intervals of the to prefll the breathing circuit and the oxygen fow was S group were prolonged at T3 (P < 0.05) while the ratio of adjusted to 2 L/min afer the patients fell asleep. Moreover, the Tp-e/QT decreased (P < 0.05). concentration in the volatilisation pot was adjusted and the third ECG was collected afer the sevofurane concentration 4. Discussion reached 1.3 MAC and was sustained for 6 min. During the research period, patients maintained autonomous respiration Sudden cardiac death (SCD) occurs in about 800,000 peo- and then they breathed via an oxygen mask afer using the ple every year, abnormal ventricular repolarisation-induced BioMed Research International 3

Table 1: A comparison of the two groups of patients under general conditions (mean ± SD).

ASA grade Age Body weight Group Cases (i.e. I/II) (Years) (kg) Pgroup 60 42/18 37±856±7 Sgroup 60 50/10 37±855±7 Data are presented as mean ± standard deviation.

Table 2: A comparison of MAP and HR of the two groups of patients at diferent times (mean ± SD).

Group Cases Index T1 T2 T3 MAP (mmHg) 76±976±773±9 Pgroup 60 HR (beats/min) 73±975±973±10 MAP (mmHg) 76±776±774±8 Sgroup 60 HR (beats/min) 74±876±974±6 Data are presented as mean ± standard deviation. (MAP= Mean arterial pressure, HR=Heart rate)

Table 3: A comparison of QT, QTc, and Tp-e intervals and the ratio of Tp-e/QT of the two groups at diferent times (mean ± SD).

Group Cases Index T1 T2 T3 QT (ms) 393.10±19.82 394.43±16.99 394.17±20.80 QTc (ms) 419.25±12.43 422.25±14.04 424.55±17.25 Pgroup 60 Tp-e (ms) 79.35±9.32 79.82±8.03 80.90±11.27 Tp-e/QT 0.20±0.03 0.20±0.02 0.21±0.03 abc QT (ms) 393.57±19.61 392.20±21.05 427.17±25.96 abc QTc (ms) 418.95±10.97 421.05±11.69 442.43±11.89 Sgroup 60 Tp-e (ms) 79.57±7.79 80.05±7. 9 1 7 7. 8 7 ±8.11 abc Tp-e/QT 0.21±0.02 0.21±0.02 0.19±0.02 Data are presented as mean ± standard deviation. a b c Compared with T1, � < 0.05;comparedwithT2, � < 0.05; compared with the P group, � < 0.05. malignant centricular arrhythmia (MVA) is the most com- of the QRS complex to the termination of the T-wave, mon reason for SCD in clinical practice [20]. Numerous representing the whole process of ventricular depolarisation drugs can trigger MVA including antibiotics [5]. Milberg et and repolarisation [14]. Easily afected by HR, QT is generally al. [21] suggested that all antibiotics can trigger abnormal represented by using a corrected QT (QTc) interval [14]. QT ventricular repolarisation and prolong the QT interval [21]. orQTcintervalprolongationisfrequentlyusedtoevaluate In 2010, the American College of Cardiology Foundation and the risk of endogenous TdP with various drugs [5, 14]. When Te American Heart Association (ACCF/AHA) indicated depolarisation is prolonged (QRS ≥120 ms), the QT interval is that the risk of torsades de pointes (TdP)signifcantly increases also prolonged so that a single prolongation of repolarisation if the QTc interval exceeds 500 ms [22]. Te mechanisms of time cannot cause arrhythmia [24]. Te transmural reentrant antibiotic-induced cardiotoxicity are manifested in the fol- is considered as the primary mechanism of arrhythmia while lowing two ways: on the one hand, antibiotics block the rapid TDR increase is regarded as an electrophysiological basis delayed rectifer potassium (Ikr)channelofcardiomyocytes; for multiple ventricular arrhythmias [22, 25, 26]. TDR refers on the other hand, there is a pharmacokinetic efect between to the electrical heterogeneity during the repolarisation of antibiotics and other drugs [23]. epicardium, endocardium, and midmyocardium, which is Preoperative antibiotic infusion can prevent postopera- shown as the Tp-e interval in a surface ECG [14, 16]. As tive infection [1–3]. Cephalosporin antibiotics are the most a quantitative index of TDR, the Tp-e interval exerts an commonly used in clinical practice [6, 8]. Moreover, as important guiding signifcance on predictions of ventricular anaesthetic also infuences the QT interval, the safety aspects arrhythmia and evaluation of the risk therein. Te conduction of using anaesthetics afer antibiotic infusion in clinical of excitation can be infuenced when the Tp-e interval is practice are worth noting. prolonged, causing reentry and even inducing TdP [25–27]. Te QT, QTc, and Tp-e intervals and the ratio of Tp-e/QT Te Tp-e interval is normally in the range of 85 ± 11 ms with an in ECG are indices refecting the ventricular repolarisation upper limit of 110 ms in white and Hispanic women [28]. Te and can predict the risk of arrhythmia to some extent [14, 16]. Tp-e interval is also afected by HR while the ratio of Tp-e/QT Te QT interval refers to the duration from the initiation maintains unchanged within the normal range of 0.15 to 0.25 4 BioMed Research International

[15, 16]. Te Tp-e interval and the ratio of Tp-e/QT are new [12]. Higashijima et al. point out that the QT interval is indices able to evaluate and predict ventricular arrhythmias shortened afer applying 1.5 mg/kg propofol to maintain [18]. anaesthesia in patients undergoing spinal surgical procedures Te QT interval is a dynamic physiological variable. [11]; however, Bolat et al. reported that anaesthesia using Te probability of QT interval prolongation increases in 30 mg of propofol exerted no signifcant infuence on the QT populations of more than 65, or less than 18 years of age, interval of patients undergoing upper abdominal endoscopy and females are more likely to sufer from QT interval [10]. prolongation than males [29, 30]. So, young, middle-aged By using sevofurane inhalation induction afer infus- females are chosen for observation. As multiple factors (e.g., ing cefuroxime, QT and QTc intervals were signifcantly autonomic nerve activity, electrolyte concentration of plasma, extended (P < 0.05). Te mechanism is probably related to and haemodynamic stability) also infuence the QT interval constraint of the slowly activated delayed rectifer potassium [29, 30], preoperative electrolyte levels in all test subjects current (Iks) by using sevofurane [16, 19, 32]; however, the were verifed as normal and no preoperative drugs were used. Tp-e interval remained unchanged and the ratio of Tp-e/QT Te haemodynamics were maintained in a stable state during decreased (P < 0.05), which implies that although 1.3 MAC theresearchtoreduceinterferenceefectsontheobserved sevofurane can extend the duration of myocardiac repolar- indices. isation, it does not increase the nonuniformity thereof. Te ATCIfortargeted4�g/mL of plasma concentration was result is consistent with the conclusion obtained by Lee et used in the P group. Te target plasma concentration rose al.totheefectthat8%ofsevofuraneusedforanaesthesia to target efect-site concentration afer 3 to 5 min, so the induction of children only prolongs QTc interval but does observation time-point was set at 5 min afer reaching the not infuence TDR [16]. Owing to sevofurane signifcantly target plasma concentration of propofol (T2). Te 1.3 MAC extending the QT interval, it is necessary to prevent the risk sevofurane was inhaled by patients in the S group. Te time of TdPwhen children with congenital LQTS are anaesthetised constant of brain tissue with sevofurane is 2 min and partial using sevofurane [5]. pressures of brain tissue and pulmonary alveoli are balanced Te study shows certain shortcomings: frstly, only female afer three times that time constant, so the time point was set patients with normal preoperative QT intervals were stud- at 6 min afer sevofurane reached 1.3 MAC (T2)[17,19,31]. ied. Considering the fact that females have a longer QT Te research results show that QT, QTc, and Tp-e intervals interval, they are more easily infuenced by drugs used to and the ratio of Tp-e/QT were unchanged afer cefuroxime prolong the interval. Terefore, the research result is probably infusion, implying that the prophylaxis infusion of single- not suitable for application among male patients. Secondly, dose cefuroxime of 1,500 mg has no efect on ventricular afer infusing cefuroxime, propofol with 4 �g/mL of target repolarisation. Chen et al. showed that the QTc interval is controlled concentration of plasma, and sevofurane with signifcantly prolonged afer healthy volunteers take 400 mg 1.3 MAC was used; however, the infuence of propofol with of moxifoxacin [4] and Kazuhiro et al. suggested that the diferent doses or sevofurane with diferent concentrations QT interval can increase afer 10 mg/kg of ciprofoxacin is on ventricular repolarisation afer infusing cefuroxime was infused in guinea pigs by intravenous injection [6]. In spite not further explored. Tirdly, the safety of using anaesthesia of this, Shampa et al. found that single-dose prophylaxis during operations in patients with long QT intervals or infusion of 2,000 or 3,000 mg of cefaroline and 2,000 mg having other antibiotic infusions before operations remains of avibactam in healthy women does not infuence the QT to be further studied. interval [8]. Moreover, Riccobene et al. also revealed that In summary, using propofol and sevofurane afer pre- single-dose prophylaxis infusion of 1,500 mg of cefaroline operativecefuroximeinfusionshownoinfuenceonTDR; in healthy women does not infuence the QTc interval [6]. however, sevofurane signifcantly prolongs ventricular repo- In the research, single-dose cefuroxime was frst used for larisation duration. Tus, it is necessary to prevent the risk of patients, which possibly did not show infuences on ven- arrhythmia in patients with prolonging QT interval or while tricular repolarisation: when infusing cefuroxime for a long using higher concentrations of sevofurane before operations. time,orrepeatedly,theinfuenceofcefuroximeonventricular repolarisationmaywellbeobserved. By using the anaesthesia induction of propofol TCI afer Data Availability infusing cefuroxime, the QT, QTc, and Tp-e intervals and > Tedatausedtosupportthefndingsofthisstudyare the ratio of Tp-e/QT remained unchanged (P 0.05). Tis available from the corresponding author upon request. indicates that using propofol as anaesthesia induction afer cefuroxime infusion cannot infuence ventricular repolarisation and disturb the stability of cardiac electrophysiology. Conflicts of Interest TeresultissimilartothatobtainedbyHume-Smithetal. on children; that is, propofol TCI at plasma concentrations Te authors declare no conficts of interest. of 3 to 6 �g/mL has no efect on QT and Tp-e intervals in healthy children [29]. Te infuence of propofol on References ventricular repolarisation is still a matter of debate [10– 12]. Kim et al. revealed that the QT interval of patients [1] I. Kaposvari,´ K. Korm¨ oczi,¨ Z. B. Laszl´ o,´ F. Oberna, F. Horvath,´ signifcantly prolongs afer propofol (5 �g/mL) TCI induction and A. Joob-Fancsaly,´ “Prospective randomized study regarding BioMed Research International 5

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