|Year : 2023 | Volume
| Issue : 1 | Page : 87-91
Comparing the bleeding control effect of labetalol, remifentanil and dexmedetomidine during craniotomy; A randomised clinical trial
Mahdi Nikoohemmat1, Hesameddin Modir2, Esmail Moshiri2, Aidin Shakeri3
1 Department of Anesthesiology, Students Research Committee, Arak University of Medical Sciences, Arak, Iran
2 Department of Anesthesiology, Clinical Research Development Center of Valiasr Hospital, Arak University of Medical Sciences, Arak, Iran
3 Department of Neuroscience, Clinical Research Development Center of Valiasr Hospital, Arak University of Medical Sciences, Arak, Iran
|Date of Submission||26-Mar-2022|
|Date of Acceptance||27-Sep-2022|
|Date of Web Publication||24-Nov-2022|
Dr. Hesameddin Modir
Clinical Research Development Center of Valiasr Hospital, Arak University of Medical Sciences, Arak
Source of Support: None, Conflict of Interest: None
Introduction: Blood loss management in craniotomy is essential for a patient's haemodynamic stability and a significantly better view of the surgical site. The study aimed to address the comparative efficacy of labetalol (LAB), remifentanil (REM) and dexmedetomidine (DXM) on the bleeding control during the craniotomy procedure. Materials and Methods: In a double-blind trial, ninety patients eligible for undergoing craniotomy were recruited and assigned to DXM, LAB and REM groups by the block-randomised method. The vital signs, including heart rate (HR), mean arterial pressure, and oxygen saturation (SaO2) after induction and during the hypotension phase every 15 min until the end of surgery and at recovery and certain time points (2, 4 and 6 h post-operative), were recorded. The amount of bleeding, surgeon satisfaction and dose of propofol used, side effects and haemoglobin level before and 12 h after surgery were registered. Data analysis was conducted using the SPSS software by one-way analysis of variance, repeated measurement test and Chi-square test at a significance level of 0.05. Results: No significant difference was found in vital signs, including SaO2, blood pressure, HR, duration of surgery, extubation time and the amount of propofol consumed, side effects and haemoglobin level (P > 0.05). Nevertheless, the DXM group showed a prolonged recovery time (P = 0.018), less bleeding (P = 0.001) and the highest surgeon satisfaction (P = 0.001) when compared with other groups. Conclusion: Our results showed that DXM helps increase surgeon satisfaction and reduce bleeding while increasing the recovery time. Overall, it does, however, have improved performance without any side effects, based on which DXM can hence be recommended to be used to control bleeding during craniotomy.
Keywords: Bleeding control, craniotomy, dexmedetomidine, labetalol, remifentanil
|How to cite this article:|
Nikoohemmat M, Modir H, Moshiri E, Shakeri A. Comparing the bleeding control effect of labetalol, remifentanil and dexmedetomidine during craniotomy; A randomised clinical trial. Adv Hum Biol 2023;13:87-91
|How to cite this URL:|
Nikoohemmat M, Modir H, Moshiri E, Shakeri A. Comparing the bleeding control effect of labetalol, remifentanil and dexmedetomidine during craniotomy; A randomised clinical trial. Adv Hum Biol [serial online] 2023 [cited 2023 Feb 7];13:87-91. Available from: https://www.aihbonline.com/text.asp?2023/13/1/87/361969
| Introduction|| |
Bleeding and subsequent control continue to be common in all surgeries due to its importance for the limited visual field of the microscope. Discontinued bleeding and exceeding a certain threshold may cause disturbances and haemodynamic instability, and consequently, a decreased oxygen-carrying capacity of the blood, hypotension, cardiac output, reduced perfusion of vital organs, adverse effect of surgical field bleeding on the vision of the surgeon, prolonged time of surgery, need for blood transfusions and damage to sensitive structures near the surgery site.,,
Prevention of blood loss is a chief consideration in craniotomy, although less studied than hip and knee arthroplasty. Blood loss management in craniotomy is essential for a patient's haemodynamic stability and a significantly better view of the surgical site., Furthermore, the management of craniotomy is of paramount significance owing to the proximity of important and very fragile nerve structures. Medications such as labetalol (LAB), clonidine, dexmedetomidine (DXM), nitroglycerin, tranexamic acid and remifentanil (REM) are widely applied to control surgical bleeding,, among which the third is well known as a highly selective α2-adrenergic receptor agonist, with sedative, amnestic and analgesic properties and used in septoplasty, being able to reduce bleeding.,
DXM appears to reduce the intra- and post-operative need for opioids and has predictable sympatholytic effects, which can help reduce the response to surgical stress and to maintain a stable haemodynamic status., The results of recent studies showed no strong evidence to support DXM as an option for all patients, and the decision to infuse the drug should be made with caution based on the anaesthesiologist's opinion and the patient's intraoperative condition. Although it has been shown that DXM can effectively prevent bleeding more than the other drug and cause lower blood pressure (BP) and heart rate (HR) in patients, it is associated with a prolonged recovery time.
LAB, a new adrenergic receptor antagonist (β1, β2 and α1), is used for induction of hypotension, whose targets in β-receptors are more specialised five to ten times more than other receptors and is therefore used in the management of tachycardia. Some studies showed that REM is related to fewer side effects, lower narcotics usage and shorter recovery time compared to LAB. Moreover, when comparing LAB and DXM, it has been found that LAB can more effectively control bleeding with a higher incidence of side effects, such as nausea, vomiting and chills.
REM is a new ultra-short-acting phenylpiperidine opioid analgesic agent with a unique pharmacokinetic profile that is widely used for general anaesthesia. High doses of REM help improve intraoperative haemodynamic stability without any delay in recovery from general anaesthesia,, and reduce intraoperative bleeding., Patients treated with REM have been reported to have lower intraoperative systolic and diastolic BP than those sedated with fentanyl.
The surgical field during craniotomy should be free from bleeding or with as little bleeding as possible for a better vision during surgery. Considering the different outcomes from previous studies and a lack of a three-group comparative study on the administration of LAB, DXM and REM for bleeding control during craniotomy, the present trial was designed to compare these to finally use one or all the three drugs with better effect or fewer complications, if the desired results were achieved.
| Materials and Methods|| |
Study setting and patients
A double-blind, randomised clinical trial recruited ninety eligible patients undergoing craniotomy at the Valiasr Hospital, Arak, Iran, after obtaining written informed consent and verification of inclusion and exclusion criteria. Sample size calculation was conducted based on the results of other same study results and considering study power; 1−β = 80%, and type one error; α = 0.05. Available sampling was performed for the recruitment of eligible patients.
Inclusion criteria included age between 18 and 75 years, American Society of Anesthesiologists class I and II, no coagulation disorders, no history of cardiovascular disease, proper BP control, no history of opioid abuse, being scheduled for craniotomy, plasma creatinine ≤1.5 mg/dL, and platelet count more than 150,000/mm3. Exclusion criteria included pregnancy, BMI ≥35kg/m2, sensitivity to the drugs studied, family history of thromboembolism, and patient dissatisfaction with participation in the study.
All patients were hospitalised for 1 day and were nil per os for eight hours prior to surgery. After recording the demographic information, two IV lines were inserted in different areas: one to inject the drugs studied and another for the administration of serum and other drugs. HR, mean arterial pressure (MAP) and oxygen saturation (SaO2) were measured before induction. At the beginning of induction, 5 ml/kg of crystalloid fluid was infused, and 100% oxygen was administered to patients through the mask. Thirty μg/kg midazolam and 2 μg/kg fentanyl were given intravenously as a premedication. Subjects were administered 2.5 mg/kg propofol and 0.5 mg/kg atracurium to induce general anaesthesia, followed by endotracheal intubation with an appropriate size endotracheal tube. The patient was then mechanically ventilated to maintain an exhaled carbon dioxide concentration of 30–35 mmHg and a SaO2 of 98%. Anaesthesia was maintained with oxygen and nitrous oxide (50:50) and isoflurane 1%, with 10 mg of atracurium injected every 20–30 min. Moreover, the infusion of propofol at a dose of 50–150 μg/kg/min was set up to stabilise anaesthesia and achieve controlled hypotension. Controlled hypotension is defined as a 20%–30% reduction of baseline MAP.
Patients were assigned to three groups using block randomisation with a block size of 6. The intervention drug was administered by bolus injection; after induction of anaesthesia and endotracheal intubation and before surgery, the bolus dose of the intervention drug was calculated for each group, diluted to 10 mL and slowly administered over 10 min. The infusion dose of the intervention drug was calculated and infused by an infusion pump MEDIMA S1 (B Braun AG, Germany) throughout the surgery.
The REM group received a bolus dose of 10 ml of normal saline for 10 min and then REM GlaxoSmithKline, London, UK) at a dose of 0.1 μg/kg/min until the end of surgery. The DEX group was given 1 μg/kg of DXM (Iran Eksir, Tehran, Iran) for 10 min as a loading dose, followed by 0.4–0.8 μg/kg/h as a maintenance dose. And the LAB group received 0.25 mg/kg IV LAB (Kern Pharma SL, Spain) for 10 min as a loading dose, followed by 1–2 mg/kg/h as a maintenance dose.
HR, MAP and SaO2 were measured and recorded after induction and during the hypotension phase every 15 min until the end of surgery and in recovery and 2, 4 and 6 h after surgery. The surgeon, who was blind to patient groupings of the study and had no information on anaesthesia drugs, assessed the surgical site for bleeding based on the satisfaction scoring system (0–5), including 0: no bleeding; (1) very mild bleeding, which can be considered as dry; (2) mild bleeding that does not distort the cut area; (3) moderate bleeding which affects the area; (4) severe bleeding which can be controlled but destroys it and (5) very severe bleeding that cannot be controlled. A score of ≤2 is a favourable bleeding score for the surgical site. Moreover, surgeon satisfaction was coded as 0 (bad), 1 (average) and 2 (good). Time to extubation was determined by proper respiration volume and airway reflex return, and the patient's recovery discharge criterion was assessed by Aldrete score, i.e., to obtain a score of 9 or higher. These were recorded on the patient's assessment form, and then the patients were transferred to the ward if they gained a score of 9 or higher.
In the case of intraoperative side effects, for instance, hypotension (mean BP of <60 mmHg), the action was taken to control the pressure first by reducing the dose of anaesthetic drugs and increasing the volume of crystalloid serum administered. In the case of stable bradycardia (HR less than 50/min), 0.5 mg of intravenous atropine was also given and recorded; post-operative complications such as nausea/vomiting, chills, bronchospasm, headache, dizziness, blurred vision and sore throat were recorded. In the case of the need to use other antihypertensive drugs during the surgery, it was included in the assessment form, and the patient was excluded from the study. The patient's haemoglobin level was measured and recorded before and 12 h after surgery.
All subjects were informed about the study objectives, and the informed consent form was signed by all patients. Moreover, the study protocol was approved by the ethical committee of Arak University of Medical Sciences, and the ethics committee reference number is IR.ARAKMU.REC.1400.052 at 13-06-2021. In addition, the project protocol was registered and approved by the Iranian Registry Clinical Trial by IRCT registration number of IRCT20141209020258N167.
Data collected were analysed by Statistical Package for the Social Sciences (SPSS) software version 20 (SPSS Inc., Chicago, IL, USA) using descriptive and analytic statistics. Data analysis was conducted using the SPSS software by one-way analysis of variance, repeated measurement test and Chi-square test. Tukey post hoc test was used for pairwise comparison among the three groups.
| Results|| |
In this double-blind, randomised clinical trial, ninety patients undergoing craniotomy were randomly split into three equal groups of LAB, DEX and REM. The mean age of the patients was 39.12 ± 9.78 years and varied from 24 to 65 years. The mean body mass index was 22.81 ± 2.44, and gender distribution showed that 51 (56.7%) were male and 39 (43.3%) were female. Participants were matched for age, gender and body mass index. No statistically significant difference was observed in HR [Chart 1], BP [Chart 2], SaO2 [Chart 3], duration of surgery, extubation time, propofol use, side effects and haemoglobin level among the three groups (P > 0.05). Moreover, the analysis of variance for repeated measurements showed that there was no significant difference among the groups in the trend of haemodynamic parameters, including HR [Chart 1], BP [Chart 2], and SaO2 [Chart 3].
As shown in [Table 1], statistically significant differences were found in recovery time (P = 0.018) and in bleeding score (P = 0.001) among the groups. The post hoc analysis showed a more prolonged recovery time in the DEX group in comparison to the LAB and REM groups. Moreover, the bleeding score was statistically lower in the DEX and REM groups than that of the LAB group. In addition, statistically significant differences were observed among the three groups in terms of surgeon satisfaction (P = 0.001) and the greatest level was found in the DEX group [Table 2].
|Table 1: Comparison of the mean of recovery time and bleeding score among labetalol, dexmedetomidine and remifentanil groups|
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|Table 2: Comparison of the mean of surgeon satisfaction level among labetalol, dexmedetomidine and remifentanil groups|
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| Discussion|| |
Our results showed no statistically significant difference among the three groups in terms of SaO2, BP, HR, duration of surgery, extubation time, propofol use, side effects and haemoglobin level (P > 0.05). Recovery time was longer in the DEX group, while the lower bleeding and the highest level of surgeon satisfaction was in the DEX group. Overall, DXM increased recovery time and surgeon satisfaction and reduced bleeding. As reported by Ayoglu et al.'s study on the efficiency of DXM in reducing bleeding during septoplasty and tympanoplasty, DXM reduced bleeding and fentanyl consumption during general anaesthesia in septoplasty. Ruku et al.'s study showed that on continuous infusion of DXM when compared to nitroglycerin, it was found that esmolol is an effective and safe way to produce controlled hypotension by achieving the target MAP, minimising blood loss and maintaining superior haemodynamics in posterior spinal surgery, and compared to nitroglycerin and esmolol, nitroglycerin had a better effect on bleeding control. It is a highly selective α2-adrenergic receptor agonist with sedative, amnestic and analgesic properties, which is used in septoplasty, can reduce bleeding,, fulfils the intra and post-operative need for opioids and has sympatholytic effects, which can reduce the response to surgical stress and maintain a stable haemodynamic status. Our results were consistent with those of Ruku et al. Eghbal et al. compared the effect of LAB and DXM on intraoperative blood loss and surgical conditions in endoscopic sinus surgery and reported that LAB works better to control bleeding, while side effects, such as nausea, vomiting and chills were more commonly seen in the LAB receiving group. Our trial showed that DXM increased recovery time and surgeon satisfaction, while it decreased bleeding. Modir et al.'s study compared REM, magnesium sulphate and DXM and showed that DXM better prevents bleeding than others and causes lower BP and HR while the recovery time is prolonged.
Furthermore, as Javaherforooshzadeh et al. reported in their study comparing haemodynamic changes during the infusion of DXM and REM in lumbar discopathy surgery, no significant difference was observed in blood loss and haemodynamic changes between DXM plus propofol and REM plus propofol, but patients receiving DXM combination had fewer postoperative side effects and a lower post-operative analgesic requirement. DXM in our study helped increase recovery time, surgeon satisfaction and decreased bleeding. Similarly, Matsuura et al.'s study evaluated the effect of REM on reducing orthognathic surgery bleeding and showed that it reduced bleeding, but BP did not change in patients receiving REM, while DXM in our study increased recovery time and surgeon satisfaction and decreased bleeding. Another study Moshiri et al., aimed to compare the effects of propofol and DXM on hypotension during endoscopic sinus surgery and the amount of bleeding in the surgical field, concluding that a reduction in bleeding and maintaining an appropriate surgical field was observed, but the difference was not significant between the groups, while our study showed an increased recovery time and surgeon satisfaction and reduced bleeding with DXM.
Sajedi et al.'s study compared REM and LAB for hypotension during sinus endoscopy and showed that recovery time and pain were significantly longer in the LAB group, while patients receiving REM reported more satisfaction and fewer side effects, whereas the need for narcotics was lower and recovery time was shorter. In the present study, DXM increased recovery time and surgeon satisfaction and reduced bleeding compared to other drugs. Hadavi et al. compared the effect of LAB and nitroglycerin on surgical field quality in rhinoplasty surgery. While their study concluded that a little difference was observed in the effect of blood loss during rhinoplasty between LAB and nitroglycerin, DXM in our study could increase recovery time and surgeon satisfaction, as well as decrease bleeding.
Lee et al.'s study aimed at comparing DXM and REM for controlled hypotension and recovery in nasal sinus surgery and indicated that no statistical difference was seen in total blood loss haemodynamic parameters, time to extubation or pain relief rate. Moreover, as the sedation score was lower in the DXM group when compared to the REM group, they concluded that the post-operative recovery was faster in the second group. Though our results were consistent with theirs in terms of recovery time, DXM in our study increased surgeon satisfaction and decreased bleeding. A study by Kawano et al. on the comparison of REM and fentanyl in the management of intraoperative blood loss in spinal surgery reflected that REM, as an intraoperative adjuvant, reduces blood loss and lowers BP. Similarly, an increased recovery time and surgeon satisfaction, as well as decreased bleeding associated with DXM, was supported by the present clinical trial.
| Conclusion|| |
The results from this study showed that DXM could increase surgeon satisfaction and reduce bleeding, as well as increase the recovery time. The medication has a better performance than the other two drugs, while it causes side effects in our subjects. Hence, DXM is recommended to control bleeding during craniotomy.
This paper is the result of a thesis in general medicine. The code of ethics is IR.ARAKMU.REC.1400.052 and the clinical trial code is IRCT20141209020258N167. Hence, the authors would like to express gratitude to the Clinical Research Council at the Valiasr Hospital for its guidance and the research deputy of Arak University of Medical Sciences for his assistance and support.
Financial support and sponsorship
This study was financially supported by Arak University of Medical Sciences.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Velkers C, Berger M, Gill SS, Eckenhoff R, Stuart H, Whitehead M, et al
. Association between exposure to general versus regional anesthesia and risk of dementia in older adults. J Am Geriatr Soc 2021;69:58-67.
Schmidt-Braekling T, Goytizolo E, Waldstein W, Sharrock N, Boettner F. The effect of hypotensive anesthesia on hemoglobin levels during total knee arthroplasty. J Clin Med 2020;10:57.
Lin S, McKenna SJ, Yao CF, Chen YR, Chen C. Effects of hypotensive anesthesia on reducing intraoperative blood loss, duration of operation, and quality of surgical field during orthognathic surgery: A systematic review and meta-analysis of randomized controlled trials. J Oral Maxillofac Surg 2017;75:73-86.
Park JH, Rasouli MR, Mortazavi SM, Tokarski AT, Maltenfort MG, Parvizi J. Predictors of perioperative blood loss in total joint arthroplasty. J Bone Joint Surg Am 2013;95:1777-83.
Szpalski M, Gunzburg R, Sztern B. An overview of blood-sparing techniques used in spine surgery during the perioperative period. Eur Spine J 2004;13 Suppl 1:S18-27.
Parvizi A, Haddadi S, Faghih Habibi A, Nemati S, Akhtar N, Ramezani H. Dexmedetomidine efficacy in quality of surgical field during endoscopic sinus surgery. Iran J Otorhinolaryngol 2019;31:281-8.
Rokhtabnak F, Djalali Motlagh S, Ghodraty M, Pournajafian A, Maleki Delarestaghi M, Tehrani Banihashemi A, et al.
Controlled hypotension during rhinoplasty: A comparison of dexmedetomidine with magnesium sulfate. Anesth Pain Med 2017;7:e64032.
Modir H, Moshiri E, Naseri N, Faraji F, Almasi-Hashiani A. A randomized parallel design trial of the efficacy and safety of tranexamic acid, dexmedetomidine and nitroglycerin in controlling intraoperative bleeding and improving surgical field quality during septorhinoplasty under general anesthesia. Med Gas Res 2021;11:131-7.
] [Full text]
Modir H, Modir A, Rezaei O, Mohammadbeigi A. Comparing remifentanil, magnesium sulfate, and dexmedetomidine for intraoperative hypotension and bleeding and postoperative recovery in endoscopic sinus surgery and tympanomastoidectomy. Med Gas Res 2018;8:42-7.
] [Full text]
Lee J, Kim Y, Park C, Jeon Y, Kim D, Joo J, et al
. Comparison between dexmedetomidine and remifentanil for controlled hypotension and recovery in endoscopic sinus surgery. Ann Otol Rhinol Laryngol 2013;122:421-6.
Kawano H, Manabe S, Matsumoto T, Hamaguchi E, Kinoshita M, Tada F, et al
. Comparison of intraoperative blood loss during spinal surgery using either remifentanil or fentanyl as an adjuvant to general anesthesia. BMC Anesthesiol 2013;13:46.
Moshiri E, Modir H, Yazdi B, Susanabadi A, Salehjafari N. Comparison of the effects of propofol and dexmedetomidine on controlled hypotension and bleeding during endoscopic sinus surgery. Ann Trop Med Public Health 2017;10:721-5. [Full text]
Javaherforooshzadeh F, Monajemzadeh SA, Soltanzadeh M, Janatmakan F, Salari A, Saeed H. A comparative study of the amount of bleeding and hemodynamic changes between dexmedetomidine infusion and remifentanil infusion for controlled hypotensive anesthesia in lumbar discopathy surgery: A double-blind, randomized, clinical trial. Anesth Pain Med 2018;8:e66959.
El-Shmaa NS, Ezz HA, Younes A. The efficacy of Labetalol versus Nitroglycerin for induction of controlled hypotension during sinus endoscopic surgery. A prospective, double-blind and randomized study. J Clin Anesth 2017;39:154-8.
Sajedi P, Rahimian A, Khalili G. Comparative evaluation between two methods of induced hypotension with infusion of remifentanil and labetalol during sinus endoscopy. J Res Pharm Pract 2016;5:264-71.
] [Full text]
Eghbal A, Modir H, Moshiri E, Khalili M, Barsari FZ, Mohammadbeigi A. Hypotensive effect of labetalol and dexmedetomidine blood loss and surgical conditions in functional endoscopic sinus surgery: A double-blind randomized clinical trial. Formosan J Surg 2018;51:98-104.
Shariat Moharari R, Shahinpour S, Saeedi N, Sahraei E, Najafi A, Etezadi F, et al
. Comparison of intraoperative infusion of remifentanil versus fentanyl on pain management in patients undergoing spine surgery: A double blinded randomized clinical trial. Anesth Pain Med 2021;11:e115576.
Twersky RS, Jamerson B, Warner DS, Fleisher LA, Hogue S. Hemodynamics and emergence profile of remifentanil versus fentanyl prospectively compared in a large population of surgical patients. J Clin Anesth 2001;13:407-16.
Matsuura N, Okamura T, Ide S, Ichinohe T. Remifentanil reduces blood loss during orthognathic surgery. Anesth Prog 2017;64:3-7.
Ghodraty MR, Homaee MM, Farazmehr K, Nikzad-Jamnani AR, Soleymani-Dodaran M, Pournajafian AR, et al
. Comparative induction of controlled circulation by magnesium and remifentanil in spine surgery. World J Orthop 2014;5:51-6.
Aldrete JA. Post-anesthetic recovery score. J Am Coll Surg 2007;205:e3-4.
Ayoglu H, Yapakci O, Ugur MB, Uzun L, Altunkaya H, Ozer Y, et al
. Effectiveness of dexmedetomidine in reducing bleeding during septoplasty and tympanoplasty operations. J Clin Anesth 2008;20:437-41.
Ruku R, Jamwal A, Bhadrala N, Gulati S. Randomized open-labelled comparative evaluation of the efficacy of nitroglycerine, esmolol and dexmedetomidine in producing controlled hypotension in spine surgeries. Anesth Essays Res 2019;13:486-91.
] [Full text]
Hadavi MR, Zarei Y, Tarogh S. Comparison of effects of labetalol and nitroglycerine on intraoperative blood loss and surgical field quality in rhinoplasty surgery. World J Plast Surg 2015;4:60-5.
[Table 1], [Table 2]