Different Analgesic Routes of Magnesium Sulfate: Intravenous versus Pectoralis II Interfascial Plane Block for Breast Cosmetic Surgeries.

PURPOSE: The purpose of the study is to evaluate the most effective analgesic route of magnesium sulfate (MgSO4) either intravenous (i.v.) or pectoralis interfascial plane block. PATIENTS AND METHODS: Fifty adult female patients were divided into two equal groups: i.v. MgSO4 and Pecs II block MgSO4 (Pecs MgSO4) group. After general anesthesia, in i.v. MgSO4 group, the local anesthetic (LA) for Pecs II block was prepared by adding 3 mL saline to 57 mL bupivacaine 0.25% divided equally for each side. A bolus i.v. solution of MgSO4 10% 0.5 mL.kg-1 diluted in saline in a total volume of 100 mL was given over 15 minutes. Then, the solution for continuous i.v. infusion; 30 mL MgSO4 10% and 70 mL saline was infused at the rate of 0.5 mL.kg-1.h-1 intraoperatively. For PecsMgSO4 group, LA formed of 3 mL MgSO4 10% added to 57 mL bupivacaine 0.25%. Whereas, 100 mL saline was given as bolus i.v. followed by continuous infusion of 100 mL normal saline at the rate of 0.5 mL.kg-1.h-1.
RESULTS: In the group received MgSO4-bupivacaine Pecs II block, there was a nonsignificant decrease in postoperative morphine consumption compared to i.v. administration of MgSO4. The two groups were comparable in the intensity of pain and sedation scores.
CONCLUSION: The use of bupivacaine Pecs II block enhanced with addition of MgSO4 to pectoralis interfascial plane block or intravenously in patients underwent breast cosmetic surgeries under general anesthesia was associated with comparable results of the postoperative morphine requirements, intensity of postoperative pain, and extension of the duration of postoperative analgesia. The intraoperative hemodynamic effects i.v. MgSO4 were superior to the pectoralis interfascial plane route of administration. Copyright:

INTRODUCTION

Breast cosmetic surgeries are commonly performed surgical procedures. Pain and discomfort are common after those surgeries.[1] Regional block of the chest wall provides excellent safe analgesia resulting in reduced perioperative narcotic requirement and improvement of the pulmonary function.[23]

The Pecs II block is a superficial thoracic wall block targeting long thoracic, pectoral, intercostobrachial, and intercostal (3rd–6th) nerves applied for procedures involving the anterior chest wall. Interfascial plane is the site of local anesthetic (LA) administrated between pectorals major and minor then between pectoralis minor and serratus anterior muscles causing LA spread under the Gerdy's ligament.[4]

Many medications were used to potentiate and prolong the acute postoperative pain control. However, limited available studies concerning about multimodal analgesia had compared the efficacy of different routes of the same analgesic.[56]

One of those analgesics is magnesium sulfate (MgSO4). The addition of MgSO4 to LA in different nerve block techniques had conflicting results.[789]

Furthermore, the effectiveness of perioperative administration of intravenous (i.v.) MgSO4 as an analgesic sparing treatment is considered to be a controversial issue over the past few years.[101112]

Hence, this study aimed to spotlight the most effective analgesic route of MgSO4 either i.v. or pectoralis interfascial plane block after bilateral breast cosmetic surgery.

The analgesic consumption in the 1st postoperative day was the primary outcome, while the hemodynamics, postoperative analgesic duration, pain, and sedation scores were the secondary outcomes.

PATIENTS AND METHODS

This prospective, randomized, double-blinded study was held in the Plastic and Burn Center at Mansoura University Hospital after the approval of Mansoura Faculty of Medicine Institutional Review Board (R/17.02.130).

Fifty adult female patients, American Society of Anesthesiologists Physical Status I and II, underwent bilateral breast cosmetic surgery after informed consent were included in this study.

Patients were excluded if they were pregnant, breastfeeding, renal, hepatic, hypertensive, or had any disturbance in cardiac conductance, coagulopathy, neuromuscular disorder, or underwent previous breast surgery. Also if they had serum magnesium level >2.2 mg.dL-1, allergy to any drug used, taking within 48 h of study, and any analgesic or drugs containing magnesium or calcium channel blockers were excluded from the study.

Patients were randomly allocated via sealed-envelope technique into two groups of 25 each; i.v. MgSO4 group and Pecs II block MgSO4 (PecsMgSO4) group.

In the study, the three different solutions applied for each patient (bolus i.v., continuous i.v. infusion and LA solution) were prepared by an anesthetist who was not involved in collecting data using MgSO4 10%.

For i.v. MgSO4 group, the LA used for bilateral Pecs II block was prepared by adding 3 mL normal saline to 57 mL bupivacaine 0.25% which was divided equally for each side. A bolus i.v. solution of MgSO4 10% 0.5 mL.kg-1 (50 mg.kg-1) diluted in normal saline in a total volume of 100 mL was given over 15 minutes. Then, the solution for continuous i.v. infusion consisted of 30 mL MgSO4 10% and 70 mL normal saline was infused to the patient at the rate of 0.5 mL.kg-1.h-1 (15 mg.kg-1.h-1) till the end of surgery.

Patients in PecsMgSO4 group received LA for Pecs II block, formed of 3 mL MgSO4 10% added to 57 mL bupivacaine 0.25% subdivided for each breast. Whereas, 100 mL normal saline bolus i.v. was followed by continuous intraoperative infusion of another 100 mL normal saline at the rate of 0.5 mg.kg-1.h-1.

After careful preoperative assessment, the numerical rating score (NRS; 0–10, 0 = no pain, 10 = worst pain) was explained to all the patients. Patients were fasting 6 h for solid food and premedicated with i.v. 50 mg ranitidine.

In the operative theater, monitoring with continuous electrocardiography, noninvasive blood pressure, and pulse oximetry were started with recording of basal values of heart rate (HR) and mean blood pressure (MBP).

After preoxygenation, all patients received fentanyl 2 μg.kg-1, propofol 1.5–2 mg.kg-1, and atracurium 0.5 mg.kg-1 before tracheal intubation. Adjustment of mechanical ventilator sitting was done to preserve the end-tidal carbon dioxide tension nearly at 30–35 mmHg. Anesthesia was maintained with sevoflurane 2% in 40% inspired oxygen and increments of atracurium.

After that and according to the group, the 100 mL study i.v. bolus solution was administrated over 15 minutes besides doing bilateral Pecs II block under aseptic precautions using a high-frequency 13-MHz linear ultrasound (US) (Sonoscape, China). With passively abducted ipsilateral upper limb, the probe was placed at the lateral infraclavicular area and directed axillary to detect both the pectoralis major and pectoralis minor muscles and preserved in the view. At that point, scanning with color Doppler was done to avoid intravascular injection. A 22G needle was inserted in-plane approach in the fascial plane between the two pectoral muscles. Ten milliliters of the prepared LA was injected according to the group after negative aspiration of blood under continues US visualization of LA spread. After that, the probe was moved until the serratus anterior was identifie, then medial-to-lateral advancement of the needle was done till located between the pectoralis minor and serratus anterior muscles. Then, another 20 mL of LA was injected. After that the same steps were repeated for the other breast.

After doing bilateral Pecs II block, once the study i.v. bolus solution was finished, the solution for i.v. infusion was initiated at 0.5 mg.kg-1.h-1 and the surgery was started.

Warmed Ringer's solution was adjusted according to the hemodynamics and losses in each patient. Intraoperative HR and MBP monitoring were recorded at 3 minutes after tracheal intubation then at 5, 10, 30, 45, and 60 minutes after starting the surgery, then at the end of surgery, 1 and 4 h postoperatively. Decrease in MBP ≥20% from basal value was considered as hypotension and was managed by fluid supplementation and if no response, i.v. ephedrine incremental was given. Bradycardia was recorded when HR <50 beat/minute.

The study i.v. infused solution was stopped before the last few skin sutures. After completion the surgery and dressing, sevoflurane was discontinued and intramuscular diclofenac sodium 1 mg.kg-1 was given. Cautious clinical assessment before antagonizing the neuromuscular blockade with 0.02 mg.kg-1 atropine and 0.04 mg.kg-1 neostigmine was done, especially to the masseter muscle strength to avoid residual paralysis. Surgical duration was recorded from starting the surgery till dressing.

Time to extubation was defined as the time from the end of surgical dressing to tracheal extubation.

Values of NRS were recorded at 0, 3, 6, 12, and 24 h postoperatively. When NRS >3; i.v. morphine 0.03 mg.kg-1 was given.

Sedation was evaluated by four-point rating scale where, 1 = fully awake; 2 = somnolent, responds to call; 3 = somnolent, responds to tactile stimulation; and 4 = asleep, responds to painful stimulation at 0, 2, and 4 h postoperatively.

The consumed amount of morphine, number of analgesic requests, and analgesic duration (from finishing the surgery till the time of first analgesic request) in the 1st postoperative day were recorded. Any postoperative complications were recorded and appropriately treated.

Sample size

Based on the previous study used the same i.v. dose of MgSO4[13] and if there is truly no difference between the standard and the tried route, then 46 patients were required to be 80% sure that the lower limit of a 90% two-sided confidence interval will be above the noninferiority limit of −2.2. Allowing drop out 10% so, 25 cases were needed in each group.

Statistical analysis

Data entry and analyses were performed using SPSS statistical package version 17 (SPSS, Inc., Chicago, IL, USA). Normal distribution of data was scanned using Shapiro–Wilk's test. Continuous and parametric data were expressed as mean ± standard deviation, while nonparametric data as median (interquartile range), then Mann–Whitney test was applied. For comparing between two measurements inside the same group, paired t-test was applied. The statistical significance level was set at P < 0.05.

DISCUSSION

The main postoperative finding of this study was, in the group received MgSO4-bupivacaine Pecs II block, there was a nonstatistically significant decrease in morphine consumption in the 1st postoperative day compared the other group received i.v. administration of MgSO4 accompanied with Pecs II block with bupivacaine alone in females underwent breast plastic surgeries. The two groups were comparable in the intensity of postoperative pain and sedation scores. Further, i.v. administration of MgSO4 was associated with significant decrease in MBP; 30 minutes after the bolus dose when compared to the basal value.

Although epidural analgesia usually applied for bilateral surgical procedures, due to its associated side effect (particularly on hemodynamic and respiratory function),[14] an easier more-safer analgesic techniques had been selected for bilateral breast surgeries.[15] This was the aim of applying bilateral Pecs II block in this study.

In the current study for comparing the efficacy of different routes of MgSO4, although one group received single Pecs II block with MgSO4, the other group had a continuous intraoperative i.v. MgSO4 infusion. This was based on the fact that any i.v. bolus injection of a drug is followed by two main stages; an early fast drop in serum concentration occurs predominantly through drug distribution, then a more gradual drop is progressed.[16] The repeated systemic administration of magnesium is needed because serum magnesium crosses the blood–brain barrier through active transport. Hence, accumulative dosages are essential for adequate central nervous system (CNS) concentration to achieve the analgesic effect.[17] Therefore, many studies which evaluated the analgesic effect of i.v. MgSO4 applied continuous infusion after the bolus calculated dose.[10121819]

The analgesic effect of both i.v. and perineural route of magnesium can be illuminated by two mechanisms. Predominant mechanism is the surface charge theory, as hyperpolarization due to alternation of sodium channel gating occurred after magnesium attraction to the negatively charged outer membrane surface.[20] Another theory is the noncompetitive antagonist action of magnesium to N-methyl-D-aspartate (NMDA) receptors which located in the CNS and in the peripheral ending of the afferent nervous fibers of the muscles and skin. By blocking NMDA receptors, inhibition of both induction and continuation of central sensitization to nociceptive stimuli occurs with consequent reduction in analgesic demands.[21]

As regards analgesic effect of i.v. regimen of MgSO4, the nonsignificant increase in morphine consumption in i.v. MgSO4 group of this study might be comparable to the finding of Ko et al. study showed that i.v. MgSO4 does not reduce postoperative analgesic requirements even after 6 h continuous infusion in females underwent abdominal hysterectomy.[10] In contrast, Albrecht et al. meta-analysis[11] and Hwang et al.[12] determined that perioperative i.v. magnesium decreases the opioid consumption.

Regarding the analgesia, after the pectoralis interfascial plane block with MgSO4, the postoperative analgesic duration in the Pecs MgSO4 group of this study (median 6 h) was comparable with Mukherjee et al. (7.6 ± 1.6 h).[7] They applied the same MgSO4 dose for supraclavicular brachial plexus block.

Whereas, the postoperative analgesic duration was prolonged in Lee et al. study (11 ± 3.1 h) after administration of 200 mg MgSO4 for interscalene nerve block in arthroscopic repair of rotator cuff. This extended duration was mostly related to doubling the bupivacaine concentration (0.5%) and the epinephrine added.[9] In addition, Ibrahim and Sultan reported 9.5 ± 0.16 h postoperative analgesic duration after MgSO4 in Pecs II block.[8] Their longer duration could be due to consuming a larger dose of MgSO4 (500 mg), although they reported a more morphine consumption (6 ± 1.5 mg) than in this study (6 ± 1.5 mg).

No statistically significant differences were noted regarding the four-point sedation scale in the two groups. Besides, at the 4th h postoperatively, reservation to awake state from the magnesium sedative effect mostly occurred (1.1 ± 0.33 in i.v. MgSO4 and 1 ± 0.2 in Pecs MgSO4 group). These results are in agreement with Ryu et al.[18] and Kiran et al.[22] This could be referred to the predicted half-life of magnesium which is about 5.2 h with the peak effect around 1 h.[23]

In the present study, there was a nonsignificant change in HR values compared to the basal value and no patient developed bradycardia. This can be explained by the myocardial membrane-stabilizing effect of magnesium.[24] A similar stabilization in HR reading was recognized in Ryu et al. study using the same i.v. dose of MgSO4.[18] But in their study, a significant intraoperative decrease in the MBP occurred four times in the first 30 minutes after the bolus MgSO4 dose which was different from the present study as significant decrease occurred once after 30 minutes in the i.v. MgSO4 group. This difference could be clarified by their use of propofol–remifentanil-based total i.v. anesthesia with thecentrally mediated sympatholytic effect of both drugs with consequent further related hypotension.[2526]

Conversely, Ozcan et al. observed no hypotensive episodes with postoperative i.v. infusion of MgSO4 maintained for 48 h. This could be related to smaller dose of MgSO4 (30 mg.kg-1 bolus and 10 mg/kg/h infusion) had been administrated for patients underwent thoracotomy.[27]

The decrease in the MBP early after the bolus i.v. MgSO4 dose could be due to the ability of magnesium to reduce adrenal gland release of catecholamine resulting in vascular smooth muscle relaxation. This is anticipated mostly after faster distribution in the i.v. route.[28] The hemodynamic stability accompanied the perineural use of MgSO4 in Pecs MgSO4 group was compatible with study used two different doses of MgSO4 (125 and 250 mg) as adjuvant to bupivacaine for supraclavicular brachial plexus block.[29]

Absence of any side effects in both groups was supported by Kashefi et al. added MgSO4 to lidocaine for i.v. regional anesthesia,[30] Abd-Elsalam et al. using 200 mg MgSO4 for trans versus abdominis plane block[31] and after MgSO4 continuous i.v. infusion in Koinig et al. study.[19]

The first limitation of this study was the lack of a control group to determine whether these results are related to Pecs II block with bupivacaine singly or due to the addition of MgSO4 for i.v. or pectoralis interfascial plane block. The second limitation of this study was not measure the postoperative serum level of magnesium to connect this with the effect observed.

CONCLUSION

The use of bupivacaine Pecs II block enhanced with addition of MgSO4 to pectoralis interfascial plane block or intravenously in patients underwent breast cosmetic surgeries under general anesthesia was associated with comparable results of the postoperative morphine requirements, intensity of postoperative pain, and extension of the duration of postoperative analgesia. The intraoperative hemodynamic effects of i.v. MgSO4 were superior to the pectoralis interfascial plane route of administration.

RESULTS

Demographic data showed no significant difference between the two groups [Table 1].

Table 1

Demographic data of the studied groups

Variables	i.v. MgSO4 (n=25)	Pecs MgSO4 (n=25)	P
Age (years)	35.3±8.6	34.6±9.4	0.779
Body weight (kg)	80.1±18.1	85.8±16.9	0.262
American Society of Anesthesiologists I/II	21/4	23/2	0.384
Type of surgery, n (%)
Reduction	20 (80)	21 (84)	0.713
Augmentation	5 (20)	4 (16)
Surgical duration (minute)	145.6±43.5	148.8±40	0.788

Values are mean± standard deviation, n (%). i.v. MgSO4=Intravenous magnesium sulfate, Pecs MgSO4=Pecs II block magnesium sulfate, SD=Standard deviation

Figure 1 shows HR where there was no statistically significant change in intra- and early postoperative values compared to the basal value in the same group. No patient developed abnormal electrocardiogram changes or bradycardia.

Figure 1

Heart rate of the studied groups (values are mean±standard deviation) i.v. MgSO4=intravenous magnesium sulphate, Pecs MgSO4=Pecs II block magnesium sulphate

As regard MBP in the perioperative period [Figure 2], there was intraoperative statistically significant decrease once in i.v. MgSO4 group, 30 minutes after starting the surgery compared to its basal reading.

Figure 2

Mean blood pressure of the studied groups (values are mean±standard deviation) i.v. MgSO4=Intravenous magnesium sulphate, Pecs MgSO4=Pecs II block magnesium sulphate. *Significance in comparison with basal values in i.v. MgSO4 group

Hypotension was recorded in six patients in i.v. MgSO4 group and in three patients in pecs MgSO4 group. All those patients had improved after bolus crystalloid infusion except one patient in pecs MgSO4 group received a total 20 mg of i.v. ephedrine.

Values of four-point sedation scale in Table 2 and NRS in Table 3 demonstrated no statistically significant changes between groups.

Table 2

Four-point sedation scale of the studied groups

Postoperative time (hour)	i.v. MgSO4 (n=25)	Pecs MgSO4 (n=25)	P
0	2.1±0.72	1.8±0.74	0.18
2	1.3±0.48	1.3±0.47	0.77
4	1.1±0.33	1±0.2	0.3

Values are mean± standard deviation. Scale: 1=Fully awake, 2=Somnolent, responds to call, 3=Somnolent, responds to tactile stimulation, 4=Asleep, responds to painful stimulation. i.v. MgSO4=Intravenous magnesium sulfate, Pecs MgSO4=Pecs II block magnesium sulfate

Table 3

Numerical rating score for pain degree of the studied groups

Postoperative time (hour)	i.v. MgSO4 (n=25)	Pecs MgSO4 (n=25)	P
0	0 (1.5)	1 (2)	0.193
3	2 (1)	3 (1)	0.561
6	3 (2)	3 (2.5)	0.613
12	6 (2)	6 (4)	0.929
24	6 (5)	4 (4)	0.277

Values are median (interquartile range). Scale:0=no pain 10=worst pain. i.v. MgSO4=Intravenous magnesium sulfate, PecsMgSO4=Pecs II block magnesium sulfate

There was no statistical difference in the time to extubation between the two groups (P = 0.42) (8.6 ± 0.3 minute and 7.9 ± 3.3 minute in i.v. MgSO4 group and pecs MgSO4 group, respectively).

Table 4 shows the 1st postoperative day analgesic profile. Although there was a decrease both in morphine consumption and number of analgesic requests in pecsMgSO4 group compared to i.v. MgSO4 group, it was not statistically significant (P = 0.284 and 0.118, respectively). The analgesic duration was comparable between the two groups (P = 0.508).

Table 4

Analgesic criteria in the 1st postoperative day of the studied groups

First postoperative day	i.v. MgSO4 (n=25)	Pecs MgSO4 (n=25)	P
Analgesic duration (hour)	6 (6)	6 (6)	0.508
Number of analgesic request	2.2±0.8	1.8±0.8	0.118
Morphine consumption (mg)	5.3±2.4	4.5±2.3	0.284

Values are median (interquartile range) or mean±Standard deviation. i.v. MgSO4=Intravenous magnesium sulfate, Pecs MgSO4=Pecs II block magnesium sulfate

No postoperative side effects were observed in all patients in the two groups.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.