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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 32  |  Issue : 2  |  Page : 411-416

Magnesium sulfate versus dexmedetomidine as adjuvants to bupivacaine in postoperative epidural analgesia after total knee replacement


Department of Anesthesia, ICU and Pain Management, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission01-Mar-2016
Date of Acceptance03-Jun-2016
Date of Web Publication25-Jun-2019

Correspondence Address:
Amany A Sultan
Department of Anesthesia, ICU and Pain Management, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_56_16

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  Abstract 

Objective
The purpose of this study was to evaluate magnesium sulfate (MgSO4) or dexmedetomidine combined with bupivacaine versus bupivacaine for postoperative epidural analgesia in patients undergoing total knee replacement (TKR).
Background
Epidural analgesia after TKR is an effective widely used technique. Plain bupivacaine is one of the commonly used drugs. Several adjuvants are emerging to enhance its analgesic properties and decrease possible side effects. MgSO4 and dexmedetomidine are promising.
Patients and methods
This prospective randomized controlled study included 60 patients undergoing TKR who were randomized into three groups for postoperative epidural analgesia: group B bupivacaine, group BM bupivacaine plus MgSO4, and group BD bupivacaine plus dexmedetomidine. Patients received first dose in the postanesthetic care unit and top-up doses were administered if patients had visual analog score greater than 4. The three groups were compared as regards analgesic efficacy, hemodynamic stability, and possible complications.
Results
No statistically significant difference was found between the three groups as regards patient demographics (age, sex, and the American Society of Anesthesiologists score). Group BD showed superior analgesic criteria with onset at 8.25 ± 1.1 min versus 9.8 ± 1.5 min in group BM and 10.1 ± 1.3 min in group B (P = 0.0002). Earliest peak analgesic effect was noticed in group BD at 14.5 ± 1.2 min versus 16.5 ± 1.6 min in group BM and 16.3 ± 1.5 min in group B (P = 0.0003). Time to top-up dose was longest in group BD (230.4 ± 26.7 min) versus 283.6 ± 32.5 min in group BM and 362 ± 50.1 min in group B (P = 0.0001). Patients in the three groups were hemodynamically stable, apart from four patients in group BM who developed hypotension requiring support (P = 0.01).
Conclusion
Dexmedetomidine and MgSO4 are safe adjuvants to bupivacaine in post-TKR epidural analgesia. Dexmedetomidine has superior analgesic characters and hemodynamic stability.

Keywords: analgesia, epidural, total knee replacement


How to cite this article:
Yehia MF, Ahmad AEA, Esmaeil EA, Eskandar AM, Sultan AA. Magnesium sulfate versus dexmedetomidine as adjuvants to bupivacaine in postoperative epidural analgesia after total knee replacement. Menoufia Med J 2019;32:411-6

How to cite this URL:
Yehia MF, Ahmad AEA, Esmaeil EA, Eskandar AM, Sultan AA. Magnesium sulfate versus dexmedetomidine as adjuvants to bupivacaine in postoperative epidural analgesia after total knee replacement. Menoufia Med J [serial online] 2019 [cited 2019 Sep 16];32:411-6. Available from: http://www.mmj.eg.net/text.asp?2019/32/2/411/260897




  Introduction Top


Perioperative pain management is a medical and human necessity, and the awareness of pain management has grown rapidly within the last two decades[1].

The proper management affects postoperative rehabilitation, morbidity, and even mortality. Moreover, proper pain management is associated with better patient satisfaction and decreased hospitalization time and cost[2].

Although local anesthetics are the foundation of regional anesthesia, they carry some disadvantages. This leads to the development and the use of a wide variety of adjuvant agents to be used with them, to enhance and prolong their actions. This allows decreasing total consumption of the used drugs and accordingly the suspected side effects[3].

These adjuvants are compounds that have undesirable or low potency effect, but in combination with local anesthetics and opioids allow reducing their dose. Many adjuvants are used in regional anesthetic practice. The most commonly used adjuvants are opioids, α2 adrenoceptor agonists (such as dexmedetomidine and clonidine), N-methyl-D-aspartate antagonists [such as ketamine and magnesium sulfate (MgSO4)], and acetylcholinesterase inhibitors (neostig mine)[4],[5].

MgSO4 was shown to have N-methyl-D-aspartate antagonistic properties in in-vitro studies[6]. Intrathecal MgSO4 has shown to potentiate morphine antinociception in a postoperative model. Several studies documented the beneficial effect of epidural and intrathecal MgSO4 in improving postoperative analgesia in several procedures, including cesarean section and thoracic surgery[7],[8],[9].

Dexmedetomidine is a highly selective α2 adrenoceptor agonist with a selectivity ratio of 1600: 1 (α2: α1). It is the pharmacologically active dextroenantiomer of medetomidine. Because of its α2 adrenoceptor agonist properties, dexmedetomidine has a broad range of pharmacological properties, including sedation associated with arousability and orientation and without respiratory depression[10],[11]. Additional effects include analgesia, anxiolysis, hemodynamic stability, antishivering effect, reduced nausea and vomiting, and anesthetic-sparing effect[12].

Objective

Our study was designed to explore whether dexmedetomidine or MgSO4 as an adjuvant to bupivacaine has better analgesic properties when compared with plain bupivacaine in post-total knee replacement (TKR) epidural analgesia.


  Patients and Methods Top


This double-blind randomized study was conducted between January 2012 and December 2014 comparing plain bupivacaine and bupivacaine plus one of the two adjuvant drugs through epidural in postoperative pain control after TKR.

Approval for study protocol was obtained from the local university ethical committee. Patients included in the study received information about the nature of the study and possible benefits and complications of the intervention and signed an informed consent form. Randomization was carried out using a computer-generated list of three equal groups; each group comprised 20 patients. A list of 60 patients was created with patient number and the group he or she was allocated to. Drug solution was prepared and administered by an anesthetist other than the one concerned with the study. Both the patient and the anesthetist taking the measures were blinded to the study drugs.

All patients received standard preoperative monitoring, premedication, and spinal anesthesia. Under aseptic conditions, infiltration of local anesthetic using an 18 G Tuohy needle at the L3–L4 space was carried out; the epidural space is identified using the loss of resistance technique, and an epidural catheter was advanced to a depth of 5 cm.

Once surgery was finished, the patient was moved to the postanesthetic care unit for recording of baseline vitals and activation of epidural analgesia.

Group B received plain bupivacaine 0.5% (2.5 ml)+7.5 ml normal saline (producing 10 ml of bupivacaine; 0.125%). Group BM received plain bupivacaine 0.5% (2.5 ml)+MgSO4 10% (0.5 ml) (50 mg MgSO4)+7 ml normal saline (producing 10 ml of bupivacaine; 0.125%), and group BD received plain bupivacaine 0.5% (2.5 ml)+dexmedetomidine 0.25 mg/kg + volume completed to 10 ml using normal saline (producing 10 ml of bupivacaine; 0.125%). Patients received epidural on demand when the visual analog scale reached 4.

Our measures included analgesic efficacy, including the onset, peak, and duration of analgesia (measured using the visual pain scale), hemodynamic stability [heart rate (HR), arterial blood pressure, and respiratory rate (RR)], motor blockade using the Bromage scale, and sedation using sedation score. Adverse effects and complications were recorded. Measurements were taken at activation and every 5 min until the patient was stable and then every 4 h. Blood cortisol level was measured in the morning on the day of surgery and repeated 1 h postoperatively and in the morning on postoperative day 1.

Statistical analysis

Data were collected, tabulated, and analyzed statistically. We used the χ2-test for nominal data and the Kruskall–Wallis test for numerical data. Statistical analysis was performed using Stata software (Stata Statistical Software: Release 12, 2011; Stata Corp., College Station, Texas, USA). We used a P value of 0.05 or less as significant and a P value of more than 0.05 as nonsignificant.


  Results Top


In our study, there was no statistically significant difference between the three groups as regards recorded demographic data (age, sex distribution, the American Society of Anesthesiologists score, and weight). The majority of patients were elderly, with a mean age of 60.1 ± 5.8 years for group B, 62.4 ± 4.2 years for group BM, and 60.8 ± 4.4 years for group BD [Table 1].
Table 1: Demographic data of the three groups: age, sex, the American Society of Anesthesiologists score, and weight distribution

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On comparing analgesic characters among the three groups, group BD showed superior results with earlier onset, peak, and longer duration of analgesia. There was a statistically significantly lower total bupivacaine consumption and less need for rescue analgesic in group BD.

In our study, group BD showed statistically significantly early onset at 8.25 ± 1.1 min versus 9.8 ± 1.5 min in group BM and 10.075 ± 1.3 min in group B (P = 0.0002). Moreover, with regard to achieving peak analgesic effect, group BD showed the earliest peak at 14.45 ± 1.2 min versus 16.5 ± 1.6 min in group BM and 16.3 ± 1.5 min in group B (P = 0.0003). Time to need top-up dose in the epidural was longest in group BD (230.4 ± 26.7 min) versus 283.6 ± 32.5 min in group BM and shortest in group B at 362 ± 50.1 min (P = 0.0001). This led to lowest total bupivacaine consumption in group BD (93.75 ± 15.9 mg), followed by group BM (120.6 ± 16.85 mg) and 151.8 ± 18.26 mg in group B (P = 0.0001) [Table 2].
Table 2: Analgesic characters in three groups

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There were no complications in the three groups, with minimal hemodynamic instability. Only four patients in group BM developed hypotension [mean arterial pressure (MAP)<75 mmHg] requiring support (P = 0.01). MAP was lowest in group BM with a mean of 86.4 ± 3.4 versus 94.5 ± 2.6 in group BD and 95.4 ± 2.1 in group B; the difference was statistically significant (P = 0.01) [Figure 1].
Figure 1: Mean arterial pressure (MAP) 4-h follow-up.

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HR was stable and no patient developed persistent bradycardia (HR < 60) or tachycardia (HR > 100). There was no statistically significant difference between the three groups as regards HR. The mean HR was 93.5 ± 2.3 beats per minute in group BM, 73.6 ± 5.4 beats per minute in group BD, and 92.7 ± 3.8 beats per minute in group B [Figure 2].
Figure 2: Heart rate (HR) 4 h follow-up.

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Drugs used at low dose (analgesic dose) are well tolerated and have minimal side effects. In our study, no patient developed sedation, motor block, or respiratory depression (RR <10/min). There were no allergic reactions to any of the drug used and no patient developed neurological complications. Three patients developed nausea and vomiting in group BM versus one patient in group BD and group B. The incidence of shivering was higher in group B as four patients developed shivering, compared with one patient in group BD and no patient in group BM. The differences were statistically nonsignificant for both shivering and nausea and vomiting. Cortisol level showed a sharp rise in the three groups 1 h postoperatively and returned to near normal levels 24 h postoperative in the three groups. There was no statistically significant difference between the three groups preoperatively, 1 h postoperatively, and 24 h postoperatively [Table 3].
Table 3: Cortisol level

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  Discussion Top


Analgesia after TKR is an integral part of patient management. Proper postoperative analgesia allows early physiotherapy, which improves the surgical functional outcome and decreases rigidity and postoperative neuropathic pain[13],[14].

Epidural analgesia has several advantages that make it a good option for postoperative pain control after TKR. It has excellent safety profile with minimal systematic effect and is well tolerated in patients with renal, cardiac, or respiratory impairment. Its pain control is excellent, with minimal effect on patient cognition and motor power. The incidence of neurological or systemic side effects is minimal[15],[16].

The majority of patients were elderly, with a mean age of 60.1 ± 5.8 years for group B, 62.4 ± 4.2 years for group BM, and 60.8 ± 4.4 years for group BD. These results are in accordance with several reports that showed a high mean age for patients undergoing TKR. Kumar et al.[17] reported a mean age of 65.8 years in more than 800 patients who underwent TKR. Similar results were reported by Ibrahim et al.[18], who revised British joint replacement register between 1991 and 2004. However, there was no statistically significant difference among the three groups as regards weight, with a mean weight of 90.5 ± 9.1 kg in group B, 88.1 ± 9.4 kg in group BM, and 93.6 ± 8.9 kg in group BD. Patients who were overweight were more prone to TKR and this is in accordance with published TKR series. Sawalha et al.[19]reported a mean weight of 86 kg in 1060 TKR performed between April 2009 and July 2013.

On comparing analgesic characters among the three groups, group BD showed superior results with earlier onset, peak, and longer duration of analgesia. There was a statistically significantly lower total bupivacaine consumption and less need for rescue analgesic in group BD.

In our study, group BD showed statistically significant early onset at 8.25 ± 1.1 min versus 9.8 ± 1.5 min in group BM and 10.075 ± 1.3 min in group B (P = 0.0002). Moreover, as regards achieving peak analgesic effect, group BD showed earliest peak at 14.45 ± 1.2 min versus 16.5 ± 1.6 min in group BM and 16.3 ± 1.5 min in group B (P = 0.0003). Shahi et al.[20] compared epidural anesthesia with 14 ml of 0.5% bupivacaine along with either MgSO4 50 mg or dexmedetomidine 0.5 μg/kg or saline in 100 patients undergoing lower limb surgery. Patients who received bupivacaine with dexmedetomidine showed statistically significant earlier sensory block at T10 (14.6 ± 1.9 min), compared with 15.4 ± 2.1 min with bupivacaine plus MgSO4 and 19.7 ± 2.1 min with plain bupivacaine.

It seems that dexmedetomidine shortens the time needed to start and to reach peak analgesic effect not only with bupivacaine but also with other amides. Saravana Babu et al.[21] compared ropivacaine plus dexmedetomidine versus ropivacaine plus clonidine in postspinal surgery analgesia. The group that received dexmedetomidine achieved earlier onset at 7.33 ± 1.76 min and peak at 11.66 ± 2.05 min versus the group that received clonidine, which achieved onset at 8.40 ± 1.61 min and peak at 13.20 ± 2.90 min (P = 0.017 and 0.022, respectively).

In the same vein, Bajwa et al.[22] compared ropivacaine plus dexmedetomidine and ropivacaine plus fentanyl for epidural analgesia in lower limb orthopedic surgeries. Patients who received dexmedetomidine achieved earlier onset of analgesia at 7.12 ± 2.44 min and peak analgesia at 13.38 ± 4.48 min versus onset at 9.14 ± 2.94 min and peak at 16.61 ± 4.36 min in patients who received fentanyl (P = 0.016 and 0.021, respectively).

In our study, the mean time to need top-up dose in the epidural was longest in group BD at 230.4 ± 26.7 min versus 283.6 ± 32.5 min in group BM and shortest in group B at 362 ± 50.1 min (P = 0.0001). This led to lowest total bupivacaine consumption in group BD at 93.75 ± 15.9 mg, followed by group BM at 120.6 ± 16.85 mg and 151.8 ± 18.26 mg in group B (P = 0.0001).

Same finding was reported by Shahi et al.[20], who found that the mean time to need epidural top-up was longest in patients who received bupivacaine plus dexmedetomidine at 587.8 ± 64.3 min versus 266.3 ± 60.9 min in patients who received bupivacaine plus MgSO4 and 157.3 ± 23.8 min with plain bupivacaine (P < 0.001).

Saravana Babu et al.[21] found that patients who received dexmedetomidine plus ropivacaine had longer time of analgesia at 407.00 ± 47.06 min versus 345.01 ± 35.02 min in patients who received clonidine and ropivacaine (P < 0.0001).

The effect of dexmedetomidine to prolong the neural block of bupivacaine is noticed also in spinal anesthesia. Kanazi et al.[23] compared the effect of 12 mg of hyperbaric bupivacaine versus 12 mg of bupivacaine supplemented with 3 mg of dexmedetomidine and 12 mg of bupivacaine supplemented with 30 mg of clonidine in spinal anesthesia. They found longest duration before regression to S1 in the group that received dexmedetomidine (190 ± 48 min), followed by 303 ± 75 min in the group that received adjuvant clonidine and shortest duration in the group that received plain bupivacaine (272 ± 38 min) (P < 0.01).

Overall, the three groups were safe with minimal hemodynamic instability. Only four patients in group BM developed hypotension (MAP <75 mmHg) requiring support. The difference was statistically significant (P = 0.01). MAP was lowest in group BM with a mean of 86.4 ± 3.4 versus 94.5 ± 2.6 in group BD and 95.4 ± 2.1 in group B, and the difference was statistically significant (P = 0.01).

Shahi et al.[20] reported a high incidence of hypotension in the three groups as 35% of patients who received bupivacaine plus dexmedetomidine developed hypotension, versus 60% in patients who received bupivacaine plus MgSO4 minutes and 80% in patients who received plain bupivacaine, with no significant difference between the groups. This may be due to higher doses of bupivacaine they used, as they used bupivacaine 0.5% (14 ml), whereas we used bupivacaine 0.5% (2.5 ml)+7.5 ml normal saline (producing 10 ml of bupivacaine; 0. 125%).

MgSO4 has hypotensive effect when administered intrathecally as demonstrated by Joshi-Khadke et al.[24], who compared the effect of neostigmine and MgSO4 as adjuvant to bupivacaine in spinal anesthesia. As they reported that 84% of patients who received MgSO4 developed hypotension requiring vasopressor versus 48% in the neostigmine group (P = 0.02).

Drugs used with low dose (analgesic dose) are well tolerated and have minimal side effects. In our study, no patient developed sedation, motor block, or respiratory depression (RR < 10/min). There were no allergic reactions to any of the drugs used, and no patient developed neurological complications. Three patients developed nausea and vomiting in group BM versus one patient in group BD and group B. The incidence of shivering was higher in group B as four patients developed shivering versus one in group BD, and no patient developed shivering in group BM. The differences were statistically nonsignificant for both shivering and nausea and vomiting.

Several reports are in agreement with our finding of minimal complications with using analgesic dose. Megahed et al.[25] reported minimal side effects when compared with plain bupivacaine 0.125% through thoracic epidural versus ketamine intravenous plus local wound infiltration after open cholecystectomy.

Stress response is immunological, metabolic, and hormonal body response to surgical stress, including trauma, pain, and fear. Stress response can have a profound response on the outcome of surgery by inducing catabolic response, delaying healing, and predisposing to infection[26].

Several studies demonstrated the positive effect of different types of anesthesia and perioperative analgesia in modulating stress response after TKR. Adams et al.[27] showed better control of stress response in patients who received epidural analgesia versus patients who received intravenous analgesia such as PCA and patients who received three in one block. With similar pain score in the three groups and significantly lower stress markers (antidiuretic hormone, adrenocorticotropic hormone, and cortisol) in the epidural group.

In our study, the three groups showed a sharp rise in cortisol level 1 h after surgery and almost returned to normal after 24 h. There was no statistically significant difference between the three groups.


  Conclusion Top


Both dexmedetomidine and MgSO4 are safe adjuvants to bupivacaine in post-TKR epidural analgesia. However, dexmedetomidine is superior to MgSO4 and plain bupivacaine as it provides better analgesic characters (onset, peak, and duration), better hemodynamic stability, and fewer overall side effects.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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