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ORIGINAL ARTICLE
Year : 2022  |  Volume : 35  |  Issue : 3  |  Page : 1342-1349

Comparison between metoprolol and pregabalin as a premedication for controlled hypotension in spine surgery


Department of Anesthesiology and Intensive Care, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission16-Oct-2021
Date of Decision29-Dec-2021
Date of Acceptance05-Jan-2022
Date of Web Publication29-Oct-2022

Correspondence Address:
4 Mervat A Elmaghraby
Shebin El-Kom, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_207_21

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  Abstract 


Objectives
The primary outcome was to compare metoprolol versus pregabalin as oral premedication to control intraoperative hemodynamics, while the secondary outcome was to assess surgical field visibility score.
Background
Elective lumbar spine surgeries are commonly performed under controlled hypotensive general anesthesia to ameliorate intraoperative blood loss and improve surgical field visibility.
Patients and methods
A total of 40 adult patients of both sexes, American Society of Anesthesiology I physical status, aged between 18 and 50 years, scheduled for elective spinal surgery during the period from August 2019 till July 2020, were randomly divided into two equal groups of 20 patients each. Group M was premedicated with 50 mg metoprolol. Group P was premedicated with 150 mg pregabalin. Oral premedication was given 90 min before the induction of anesthesia. Heart rate and mean arterial blood pressure were recorded throughout the surgery. Surgical field visibility score, surgeon satisfaction, and incidence of complications were also recorded. Data were analyzed by the variance test.
Results
Blood pressure and heart rate were more controlled to lower acceptable degree in metoprolol than pregabalin (P < 0.001). The surgical field visibility score was more clear with metoprolol than pregabalin (P < 0.001).
Conclusion
Metoprolol was found to be more effective than pregabalin in blunting hemodynamic stress response by controlling heart rate and blood pressure to lower acceptable ranges. In addition, metoprolol provided a more clear surgical field with less blood loss than pregabalin in patients undergoing spine surgery.

Keywords: hypotensive, lumbar, metoprolol, pregabalin, premedication, spine


How to cite this article:
Elmaghraby MA, Atalla HA, El-Sharkawy OA, Bahgat NM. Comparison between metoprolol and pregabalin as a premedication for controlled hypotension in spine surgery. Menoufia Med J 2022;35:1342-9

How to cite this URL:
Elmaghraby MA, Atalla HA, El-Sharkawy OA, Bahgat NM. Comparison between metoprolol and pregabalin as a premedication for controlled hypotension in spine surgery. Menoufia Med J [serial online] 2022 [cited 2024 Mar 29];35:1342-9. Available from: http://www.mmj.eg.net/text.asp?2022/35/3/1342/359473




  Introduction Top


Excessive bleeding during spine surgery is one of the most serious problems, which affects operative field visibility and complicates the surgical approach[1]. Controlled hypotension is a crucial anesthetic technique to control bleeding and improve field visibility[2]. Beta-blockers produce the desired hypotension improving surgical field visibility[3]. Metoprolol is a cardio-selective beta-1-adrenergic receptor inhibitor, which competitively blocks beta-1 receptors with minimal or no effects on beta-2 receptors. It decreases cardiac output by negative chronotropic and inotropic effects[4].

On the other hand, pregabalin bound to gated calcium channels alters the kinetics and voltage dependence of calcium currents. By reducing calcium influx at nerve terminals, pregabalin reduces the release of several neurotransmitters, including glutamate, noradrenaline, calcitonin, gene-related peptide, and substance P, and inhibits the modulation of neuronal excitability. This is presumed to account for pregabalin's analgesic actions and good control over arterial blood pressure and blunting the stress response[5],[6].

The current study aimed to compare metoprolol versus pregabalin as a premedication to induce controlled hypotensive anesthesia by controlling the heart rate as the primary aim. The secondary aims were to assess field visibility of both groups, surgeon satisfaction, and to document the associated complications.


  Patients and methods Top


This prospective, randomized trial was carried out after obtaining institutional ethics committee approval. A written informed consent was obtained from all participants. In all, 40 adult patients of either sex, belonging to American Society of Anesthesiology grade 1, aged between 18 and 50 years undergoing elective lumber discectomy surgeries under general anesthesia were included in the study during the period from August 2019 till July 2020.

Patients with any of the following were excluded from the study: hypertension, hepatic or renal disease, diabetes mellitus, bronchial asthma, pregnancy, coagulation disorders, anemia (hemoglobin <10 g/dl), ischemic heart disease, drug or alcohol abuse, allergy to any of metoprolol or pregabalin, history of beta blockers, calcium channel blockers, tricyclic antidepressants, anticoagulants, or clonidine intake.

Randomization of patients was made by a computer-generated program into two equal parallel groups of 20 patients in each. Group M was administered 50 mg metoprolol tartars (lopresor 50 mg; Novartis, Basel, Switzerland) each. Group P was premedicated with 150 mg pregabalin (lyrica 150 mg; Pfizer, New York, United States). Oral premedication was given with a sip of water 90 min before the induction of anesthesia. Preoperative assessments in all patients included medical history, general physical examination, a more detailed examination of the airway, and routine laboratory investigations. Before the procedure, patients were instructed to fast for 8 h for solids and more than 2 h for clear water. On arrival to the operating room, ECG, noninvasive blood pressure, pulse oximetry, and bispectral index (BIS) monitors were applied and baseline parameters were recorded. An 18-G cannula was secured, and a lactated Ringer's infusion (6 ml/kg/h) was started. Thereafter, anesthesia was induced with fentanyl (1 μg/kg) followed by propofol 10 mg boluses till BIS dropped below 50 marking loss of consciousness; rocuronium (0.9 mg/kg) was used to facilitate orotracheal intubation and mechanical ventilation. After induction, anesthesia was maintained with isoflurane 1.2% in a mixture of air: oxygen (1: 1). Meanwhile, the patients were mechanically ventilated targeting ETCO2 of 35–40 mmHg, and isoflurane MAC was adapted to keep BIS 40–50. After induction of anesthesia and intubation the patient was turned prone on a framework to minimize intraabdominal pressure. Arterial blood pressure was controlled to lower acceptable levels, if it increased [minimum mean arterial blood pressure (MAP) of 60–70 mmHg], 0.5 μg/kg fentanyl was given, if still uncontrolled 0.3 μg/kg/min sodium nitroprusside by a syringe pump was administered. At the end of surgery, the patient was returned to the supine position; the residual neuromuscular block was reversed with neostigmine (0.02–0.05 mg/kg) after atropine 0.015 mg/kg intravenous. The endotracheal tube was removed after attaining the accepted global and respiratory criteria for extubation. Then the patient was transferred to the PACU to be discharged to the ward at with a modified Aldrete score more than 9[7].

Hemodynamics parameters such as heart rate, MAP, oxygen saturation, and axillary cutaneous temperature probe was recorded every 5 min in the operative room.

Surgical field visibility score (Fromm and Boezaart score) was used to evaluate the quality of the operative field during surgery, and surgeon satisfaction was graded as 1 = very satisfied, 2 = satisfied, and 3 = unsatisfied. Opioid and nitroprusside consumption was measured. The patients were observed for incidence of complications such as bradycardia, tachycardia, hypotension or hypertension, shivering, respiratory depression, dizziness, visual disturbance, nausea, and vomiting[8].

Sample size calculation: this study was conducted on a total sample size of 40 patients. Based on the results of Sathyamoorthy et al.[9] study who reported a 11.4 mean difference of heart rate in premedicated patients with oral pregabalin and oral metoprolol, with SD of 8.8, to achieve 5% significance level and power of 80%; the calculated sample size was 27 patients. Adding 30% to compensate for loss or dropout, the final sample size was 40 patients.

Statistical analysis: Data were collected, revised, and then analyzed using the Statistical Package for the Social Sciences (IBM SPSS) software, version 20.0. (IBM Corp., Armonk, New York, USA).

The data were presented as number and percentages for the qualitative data. Quantitative data were described using, mean, SD, range (minimum and maximum) and median. Significance of the obtained results was judged at the 5% level. Tests used χ2 test, Fisher's exact correction, t test, analysis of variance with repeated measures and post-hoc test.


  Results Top


In this study, a total of 55 patients were screened for eligibility, 15 were excluded, and 40 patients underwent randomization to 20 patients in each group [Figure 1]. The two groups were statistically comparable with regard to mean age, sex, and BMI (P > 0.05) [Table 1].
Figure 1: Consolidated standards of reporting trials flow diagram showing patient progress through the study phases.

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Table 1: Comparison between the two studied groups according to demographic and surgical data

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The current study shows that the metoprolol group was more effective in stabilizing heart rate and MAP to a lower acceptable range than the pregabalin group at most of the time points of measurements (P < 0.001) [Figure 2], [Figure 3].
Figure 2: Bar charts show the distribution of the studied groups as regards heart rate.

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Figure 3: Bar charts show the distribution of the studied groups as regards MAP. MAP, mean arterial blood pressure.

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The Fromm and Boezaart score results showed that the metoprolol group provided a clearer visualized surgical field with a decrease in blood loss compared with the pregabalin group (P < 0.001) [Table 2], [Table 3].
Table 2: Comparison between the two studied groups according to heart rate

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Table 3: Comparison between the two studied groups according to mean arterial blood pressure

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Surgeon satisfaction score showed increased satisfaction in the metoprolol group than the pregabalin group with high statistically significant difference (P < 0.001) [Table 1].

The intraoperative fentanyl consumption in the pregabalin group was less than the metoprolol group without statistically significant difference as only seven patients needed an additional dose of fentanyl in the metoprolol group compared with four patients in the pregabalin group [Table 1].

There was no need of addition sodium nitroprusside in both groups.

Results showed that there were no statistically significant differences between two groups as regards the incidence of perioperative complications such as nausea, vomiting, bradycardia, tachycardia, hypotension, hypertension, respiratory depression, delayed recovery, dizziness, and visual disturbances, but the incidence of shivering was statistically decreased in the pregabalin group than the metoprolol group [Table 4].
Table 4: Comparison between the two studied groups according to different parameters (perioperative complications)

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  Discussion Top


Controlled hypotensive anesthesia is a technique used to limit intraoperative blood loss, improve operative field visibility, decrease the duration of surgery, and thus decreasing the amount of blood transfused. In spine surgery, improving the surgical field visibility is crucial due to the presence of important and easily traumatized neurological structures[10].

From the results of the current study, there was no statistical difference between the two groups regarding the duration of operation or recovery time. The controlled hypotension that was induced in patients premedicated with metoprolol and pregabalin caused an indirect decrease in the duration of surgery. This was supported by the Singh et al.[11] study, which reported a longer duration of surgery in placebo compared with the metoprolol group.

The current study showed that the metoprolol group was more effective in stabilizing heart rate and MAP to lower acceptable ranges than the pregabalin group (P < 0.001). Premedication with metoprolol is associated with selective blockage of beta-1 receptors in the heart, which consequently leads to a decrease in heart rate which is associated with lower cardiac output and blood loss.

The results of the current study are concordant with Singh et al.[11], who found that premedication with a β-blocker such as metoprolol is associated with benefits of reduction of reflex tachycardia in patients undergoing orthognathic surgery. Similarly Rahimzadeh et al.[12] reported that administration of metoprolol 50 mg 1 h before surgery induced adequate hypotensive anesthesia in patients undergoing nasal surgeries.

On the other side, Gupta et al.[13], who used 150 mg pregabalin as oral premedication before laparoscopic cholecystectomy, proved that pregabalin achieved better intraoperative hemodynamic stability, and the MAP was significantly attenuated during laryngoscopy and pneumoperitoneum. In addition, Kohli et al.[14] concluded that the same dose of oral pregabalin (150 mg) showed a statistically significant attenuation of MAP during laryngoscopy with maintaining intraoperative hemodynamic stability when compared with the control group. This perioperative hemodynamic stability induced by pregabalin could be explained by the adequate sedation and analgesia properties including the modulation of visceral pain and central sensitization[15].

The quality of the surgical field was compared in both groups according to the Fromm and Boezaart score and results showed that the metoprolol group provided a more clear visualization of the surgical field compared with the pregabalin group.

Mazy and Abo-Zeid[16] reported that using pregabalin 150 mg did not reduce intraoperative blood loss in spine surgeries. This may be attributed to the different types of spine surgeries included in their study. In addition, it was reported that pregabalin may induce thrombocytopenia after 5 days of continuous utilization[17]. Similar results were reported by Rahimzadeh et al.[12] and Sadek et al.[17] who found that metoprolol was associated with a statistically significant better quality of surgical field as compared with placebo in the patients undergoing nasal surgeries.

Sherif et al.[18] reported a better Fromm and Boezaart scale of the quality of the surgical field and postoperative pain intensity, which were much lower after pregabalin premedication in comparison to placebo. This was attributed to the inhibitory role of pregabalin on membrane voltage-dependent calcium channels, which decrease calcium influx at the nerve terminal and consequent attenuation of the neurotransmitters release producing analgesia and good control to arterial blood pressure than the placebo group.

In the current study, better surgeon satisfaction was found after metoprolol than pregabalin premedication as metoprolol provided a clearer visualized surgical field with decreased blood loss.

The current study results showed that there were no differences between the two groups regarding incidence of nausea, vomiting, bradycardia, tachycardia, hypotension, hypertension, and respiratory depression. This is concordant with the Jokela et al.[19] study which reported that pregabalin 150 mg is effective for postoperative analgesia without a significant increase in side effects such as nausea and vomiting. Similarly, Spreng et al.[20] and Jokela et al.[19] administered pregabalin 150 mg before elective lumbar single-level microdiscectomy and reported the incidence of nausea and vomiting as 0.05 and 0.090%, respectively.

Another study by Bakker et al.[21] showed that metoprolol was not associated with serious side effects such as severe hypotension, sedation, and/or severe bradycardia because of its cardio-selective effects, which inhibits its nonselective effect on other blockers, and that supported the current finding.

In this study, the incidence of postoperative shivering was statistically decreased after pregabalin premedication. This coincides with the findings of Gaballah and Abdallah[22], who reported that oral premedication with pregabalin 150 mg 30 min before hysteroscopic procedures under spinal anesthesia reduced the incidence of postspinal shivering.

In the current study, there was no statistically significant difference in the incidence of postoperative dizziness and visual disturbances between the two groups. We used pregabalin 150 mg instead of 300 mg, which was proved by many researches[15],[23],[24],[25],[26] with rare incidence of dizziness, visual disturbances. and delayed recovery.

Kohli et al.[14] reported increased incidence of dizziness after 300 mg of pregabalin versus 150 mg in patients undergoing hysterectomy under spinal anesthesia. However, in their meta-analysis Grant et al.[24] reported that increased rate of postoperative visual disturbance is associated with preoperative pregabalin more than or equal to 300 mg (respiratory rate = 3.11; 95% confidence interval, 1.34–7.21; P = 0.008) compared with a placebo. Delayed recovery was reported by White et al.[25] after pregabalin 300 mg, which was associated with a significant increase in the level of sedation before the induction of anesthesia and in the early postoperative period. They suggested that pregabalin is not a useful drug for preoperative medication in patients undergoing ambulatory surgery in that dose.

In the current study, intraoperative fentanyl requirements were lesser after pregabalin than metoprolol premedication to a statistically insignificant extent. This may be related to its analgesic effects, which spared opioid consumption. In their meta-analysis, Zhang et al.[26] reported that prescription of a single dose of pregabalin before surgery reduced opioid requirements. Similarly, Dauri et al.[27] showed that gabapentin and pregabalin reduced opioid use after surgery when compared with placebo.

In this study, there was no need for using any additional hypotensive agents such as sodium nitroprusside in both groups. This coincides with the findings reported by Mazy and Abo-Zeid[16], who found that nitroglycerin consumption was lower after pregabalin versus placebo premedication.

To the best of our knowledge, this is the first study to use metoprolol for controlled hypotension in spine surgery. Metoprolol was proved to be superior to pregabalin in controlling heart rate and MAP in the current trial.

One of the limitations of this study is that it is a single-center study and may not be representative of the general population. Second, we did not compare different doses of pregabalin that might produce the maximum effects and the least side effects, which need a bigger sample size and can determine complications and its relation to increased doses. We also did not use different dose regimens to reach the precise metoprolol regimen. Another point is the use of a fixed dose regardless of the patient body weight.


  Conclusion Top


Metoprolol was found to be associated with a more favorable hemodynamic profile and more clear visualization of surgical field than pregabalin during elective lumbar discectomy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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