|Year : 2019 | Volume
| Issue : 2 | Page : 234-242
Efficacy of adding dexmedetomidine as adjuvant with levobupivacaine in ultrasound-guided serratus plane block for modified radical mastectomy surgery
Mona Gad1, Mohamed Elmetwally2
1 Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Mansoura University, Mansoura, Egypt
2 Department of Surgical Oncology, Oncology Center, Mansoura University, Mansoura, Egypt
|Date of Submission||04-Mar-2019|
|Date of Acceptance||04-Mar-2019|
|Date of Web Publication||12-Jun-2019|
Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Mansoura University
Source of Support: None, Conflict of Interest: None
Background Women undergoing mastectomy experience severe pain postoperatively. Serratus plane block would be suitable for providing long-lasting regional anesthesia. This study was aimed to evaluate the effect of adding dexmedetomidine as adjuvant to levobupivacaine on the quality and duration of this block.
Patients and methods Patients were randomly allocated to three equal groups after induction of general anesthesia. Levobupivacaine group (L) (n=50): received levobupivacaine 0.25% in a volume of 0.5 ml/kg injected superficial to serratus muscle between it and latissimus dorsi muscle. Levobupivacaine–dexmedetomidine group (D) (n=50): received levobupivacaine of 0.25% plus 0.5 mcg/kg dexmedetomidine in a volume of 0.5 ml/kg injected superficial to serratus muscle between it and latissimus dorsi muscle. Group C (n=50), as a control group: received sham block with normal saline in a volume of 0.5 ml/kg. Time to first analgesia request and postoperative opioid consumption were the primary outcomes.
Results This study demonstrated that addition of dexmedetomidine to levobupivacaine in ultrasound-guided serratus plain block during modified radical mastectomy surgery delayed time of first analgesia request and reduced postoperative opioid consumption compared with levobupivacaine alone. Hemodynamic changes (hypotension and low heart rate) and sedation were more pronounced in dexmedetomidine group than the other two groups. Occurrence of nausea and vomiting in dexmedetomidine group is lower than the other two groups.
Conclusion The addition of dexmedetomidine as an adjuvant to levobupivacaine in ultrasound-guided serratus plain block during modified radical mastectomy surgery can give extended analgesic effect and lower postoperative opioid consumption.
Keywords: cancer breast, dexmedetomidine, levobupivacaine, serratus plane block
|How to cite this article:|
Gad M, Elmetwally M. Efficacy of adding dexmedetomidine as adjuvant with levobupivacaine in ultrasound-guided serratus plane block for modified radical mastectomy surgery. Res Opin Anesth Intensive Care 2019;6:234-42
|How to cite this URL:|
Gad M, Elmetwally M. Efficacy of adding dexmedetomidine as adjuvant with levobupivacaine in ultrasound-guided serratus plane block for modified radical mastectomy surgery. Res Opin Anesth Intensive Care [serial online] 2019 [cited 2019 Oct 15];6:234-42. Available from: http://www.roaic.eg.net/text.asp?2019/6/2/234/260140
| Introduction|| |
Cancer breast has continued to be the most common cancer affecting women . With the use of ultrasound (US) devices in anesthetic practice, newer regional techniques based on detailed knowledge of innervations of the breast have been developed, such as the pectoral nerve (Pecs) blocks I and II.
The serratus plane block (SPB), described by Blanco et al. , is a progression from the work with the Pecs I and II blocks. Local anesthesia (LA) is injected under US guidance either superficially or deep to serratus anterior muscle providing predictable and relatively long-lasting regional anesthesia, which would be suitable for surgical procedures performed on the chest wall .
Regarding the concern of the analgesic properties of dexmedetomidine, it has been suggested that spinal cord may be the main site of analgesic action of α2 adrenoceptor agonists. It seems that it produces analgesia at spinal and supraspinal level, and also it may provide analgesic effects through nonspinal peripheral mechanisms as intra-articular administration of dexmedetomidine during knee surgery gives better postoperative analgesia and prolongs its duration . This may be owing to stimulation of α2a receptors, inhibition of the nerve conduction through C and Aδ fibers, and the local release of encephalin . Levobupivacaine is a single enantiomer of the long-acting LA bupivacaine. This change in the molecular structure has resulted in levobupivacaine being a lesser arrhythmogenic and lesser central nervous system depressant than the same dose range of bupivacaine. The duration of the nerve block with levobupivacaine is much longer than with bupivacaine . It is interesting to study dexmedetomidine effect as a LA adjuvant to levobupivacaine on the quality of the US-guided serratus plain block in patients with cancer breast.
| Patients and methods|| |
This prospective, randomized double-blind study was conducted after approval by the Institutional Research Board on 150 American Society of Anesthesiologists I/II/III women, aged older than 20 years or more, undergoing modified radical mastectomy (MRM) under general anesthesia (GA) at Mansoura Oncology Center. Informed written consent was obtained from all patients in the study after ensuring confidentiality. Patients who refused, had skin infection in axilla, or had allergy to the studied drugs were excluded from the study.
A-priori G-power analysis was done to estimate study sample size. Assuming α (type I error) of 0.05 and β (type II error) of 0.1(power=90%), and based on a preliminary pilot study of 10 patients in each group in which it was observed that, there was about 20% difference between levobupivacaine (L) group and levobupivacaine-dexmedetomidine (D) group in total postoperative pethidine consumption (74 mg±24 versus 60 mg±21 respectively), 45 patients per group would be sufficient. A dropout of 10% of cases would be expected. Therefore, 50 patients were required in each of the three groups to detect this difference.
Patients were randomly allocated through sealed envelopes to three equal groups (n=50 in each group) using a computer-generated randomization schedule. L group received levobupivacaine 0.25% in a volume of 0.5 ml/kg injected superficial to serratus muscle between it and latissimus dorsi muscle. D group received levobupivacaine 0.25% plus 0.5 mcg/kg dexmedetomidine in a volume of 0.5 ml/kg injected superficial to serratus muscle between it and latissimus dorsi muscle. Group C served as a control group and received sham block with normal saline in volume 0.5 ml/kg. SPB and data collection were performed by independent anesthesiologist blinded to the group allocation.
The day before the surgery, the study protocol and serratus plain block procedure were explained to each patient. Patients were familiar with the use of visual analog scale (VAS) score, identifying 0 as no pain and 10 as worst imaginable pain. Patients fasted for 6 h before the surgery.
After routine monitoring, including ECG, noninvasive blood pressure, heart rate (HR), pulse oximetry in the preanesthesia room, peripheral intravenous cannula (18 G) was inserted. A premedication of 1–2 mg of midazolam was administered intravenously, 20 min before induction of GA, and lactated Ringer’s was infused 8 ml/kg to replenish the overnight fasting hours.
General anesthesia application
In the operating room, GA was induced using intravenous propofol at dose of 2–3 mg/kg, fentanyl intravenously 1.5 µg/kg, and atracurium 0.5 mg/kg. Patients were then mechanically ventilated to maintain end-tidal CO2 30–35 mmHg (respiratory rate=12 beats/min, tidal volume 7 ml/kg, inspiratory-to-expiratory ratio 1 : 2, positive end-expiratory pressure 5 cmH2O). In case of increase in intraoperative systolic blood pressure and HR of more than 20% of baseline for longer than 5 min, fentanyl 25 µg as rescue analgesia plus increasing isoflurane concentration was given; if no adequate response, 25 µg fentanyl per dose was given in increments.
Block intervention application
After induction of GA, with the patient in supine position and placing the ipsilateral upper limb abducted, we started the technique after skin sterilization with chlorhexidine by using a linear US probe with a frequency range of 6–13 MHz (Siemens, Los Angeles, California, USA). The probe was placed over the midclavicular region in a sagittal plane. The ribs were counted inferiorly and laterally, until the fifth rib in the midaxillary line was identified. The latissimus dorsi, teres major, and serratus muscles were identified. At that point, a 22 G spinal needle was introduced in-plane with respect to the US probe from superoanterior to posteroinferior direction. Under continuous US guidance, the LA solution was injected between serratus anterior muscle and the latissimus dorsi muscle in 5 ml aliquots with frequent aspiration to avoid intravenous injection.
Monitoring and complication management
In the operating room, monitoring was achieved by continuous ECG, arterial oxygen saturation, noninvasive blood pressure, and capnography. Bradycardia was defined as decrease in HR below 50 beats/min. Hypotension was defined as decrease in systolic blood pressure by 20% mmHg of the basal value. Bradycardia was treated by atropine 0.01 mg/kg. Hypotension was treated with intravenous 200 ml fluid bolus, but if this was ineffective or mean arterial blood pressure (MAP) was less than 60 mmHg, 5 mg boluses of intravenous ephedrine were given. Adverse effect like pleural puncture was suspected by desaturation, diminished air entry, or increased peak inspiratory pressure after the block and confirmed by chest radiography.
Data recording and outcome measures
Hemodynamic parameters were recorded before induction in the operating room, then every 15 min till the end of surgery, and then every 15 min in postanesthesia care unit (PACU) for 1 h till discharge to the ward. Same parameters were recorded at 2, 4, 6, 8, 12, 16, and 24 h postoperatively. The total pethidine requirement was calculated in all groups for 24 h, and time of first required dose of opioids analgesia was recorded. Pain was assessed by VAS immediately after surgery and every 15 min in PACU for 1 h and then at 2, 4, 6, 8, 12, 16, 24 h in ward. Intravenous ketorolac 30 mg was given if VAS for pain is at least 4 or upon the patient’s request. If VAS was still at least 4, pethidine 25 mg per dose was given till VAS was less than 3.
Postoperative adverse effects such as hypotension, bradycardia, nausea and vomiting (PONV), and pneumothorax were recorded. Hypotension was treated with intravenous 200 ml fluid bolus, but if MAP was still less than 60 mmHg, 5 mg boluses of intravenous ephedrine were given. Vomiting or persistent nausea was treated with intravenous primperan 10 mg, and if there was no response, ondansetron 4 mg was given. Ramsay sedation scale from 1 to 6 was as follows: 1=anxious, agitated, and restless; 2=cooperative, oriented, and tranquil; 3=responds to commands only; 4=brisk response to light glabellar tap or loud noise; 5=sluggish response to light glabellar tap or loud noise; and 6=no response . This was used to assess the level of sedation at the same times of VAS measurements. Total intraoperative fentanyl requirements and the number of patients who needed intraoperative fentanyl rescue analgesia were recorded. Patient satisfaction score was assessed before discharge by four-grade scale, including poor, moderate, good, and perfect.
This study considered time to first analgesia request and postoperative opioid consumption as primary outcomes and VAS, hemodynamics, intraoperative analgesia consumption, incidence of PONV, and patient satisfaction as secondary outcomes.
The collected data were coded, processed, and analyzed using SPSS program, version 14 (IBM corporation, IL, Chicago, USA). Normality of numerical data distribution was tested by Kolmogorov–Smirnov test. Normally distributed numerical data were presented as mean and SD and their comparisons in different groups were performed using one-way analysis of variance with post-hoc Bonferroni’s test. Non-normally distributed numerical data were presented as median and range and compared using Kruskal–Wallis test. Categorical data were presented as number and percentage, and their comparison was performed using Chi-square test. All data were considered significant if P value was less than 0.05.
| Results|| |
A total of 150 female patients aged older than 20 years or more completed this randomized clinical trial, with 50 patients in each group ([Figure 1]). There were no significant differences for patient’s demographic data and duration of surgery among the three studied groups ([Table 1]). Regarding HR and MAP, they were statistically significant lower in D group when compared with L and C groups from 15 min after SPB up to 8 h postoperatively and were statistically significant lower in group L when compared with group C from 15 min after SPB up to 8 h postoperatively ([Figure 2] and [Figure 3]). According to total intraoperative fentanyl requirements, there was no statistical difference between L and D groups (118.9±16.7 vs. 113±13.8 µg, P>0.05), whereas it was statistically significant lower in D group when compared with C group (113±13.8 vs. 142.5±15.3 µg, P<0.001) ([Figure 4]). Regarding the time to first request of postoperative analgesia, significantly longer duration of effective analgesia was encountered in group D in comparison with groups L and C (617±125 vs. 443±71 vs. 21.5±6.5 min; P<0.001) ([Figure 5]). Total postoperative pethidine consumption in group D when compared with L and C groups was significantly lower (61±13 vs. 86±18 vs. 151±17 mg; P<0.001) ([Figure 6]). Regarding the VAS scores at rest and with ipsilateral arm abduction, they were significantly lower during 1 h stay in PACU and at 2, 4, and 6 h postoperatively in D and L groups in comparison with C group (P<0.05). There was no significant difference between D and L groups during 1 h stay in PACU and till 6 h postoperatively. Meanwhile, VAS scores were significantly lower at 8 and 12 h postoperatively in D group compared with L group (P<0.05). Ramsay sedation scale was significantly higher in D group on arrival to PACU and till 2 h postoperatively when compared with L and C groups. Meanwhile, the scores were comparable between L and C groups. The number of patients having postoperative hypotension was significantly higher in D group when compared with the L and C groups [18 (36%) vs. 8 (16%) vs. 7 (14%); P=0.02]. The number of patients having PONV was significantly higher in D group when compared with the L and C groups [12 (24%) vs. 23 (46%) vs. 33 (66%); P<0.01]. Patient satisfaction score in D group was significantly higher compared with L and C groups. Moreover, this score was significantly higher in L group compared with C group.
|Figure 2 Perioperative heart rate (HR) values (beats/min). Data are expressed as mean±SD. *Significant for D or L groups in comparison with C group. #Significant for D group in comparison with L group. P<0.05, significant. C, control; D, levobupivacaine–dexmedetomidine; L, levobupivacaine.|
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|Figure 3 Perioperative mean arterial blood pressure (MAP) values. Data are expressed as mean±SD. *Significant for D or L groups in comparison with C group. #Significant for D group in comparison with L group. P<0.05, significant. C, control; D, levobupivacaine–dexmedetomidine; L, levobupivacaine.|
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|Figure 4 Total fentanyl requirements (µg). Data are expressed as mean±SD. *Significant for D or L groups in comparison with C group. P<0.05, significant. C, control; D, levobupivacaine–dexmedetomidine; L, levobupivacaine.|
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|Figure 5 Time of first request of postoperative analgesia (min). Data are expressed as mean±SD. *Significant for D or L groups in comparison with C group. #Significant for D group in comparison with L group. P<0.05, significant. C, control; D, levobupivacaine–dexmedetomidine; L, levobupivacaine.|
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|Figure 6 Total requirement of pethidine (mg) (mean and SD). Data are expressed as mean±SD. *Significant for D or L groups in comparison with C group. #Significant for D group in comparison with L group. P<0.05, significant. C, control; D, levobupivacaine–dexmedetomidine; L, levobupivacaine.|
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| Discussion|| |
The findings of this study demonstrated that addition of dexmedetomidine to levobupivacaine in US-guided serratus plain block during MRM surgery was effective and safe technique as it provided significantly prolonged time to first analgesic request, more significantly reduced the opioid consumption, and statistically significant lower postoperative pain score and PONV than using levobupivacaine alone.
Regional anesthesia techniques provide better-quality acute pain control and subsequently less chronic pain after MRM . Moreover, adequate control of acute pain preserves the immune function via suppressing the stress response to surgery and decreasing the requirements for opioids particularly morphine which can inhibit cellular and humoral immune functions . This effect may contribute in the higher rates of local recurrence after surgery and/or development of metastasis .
With the use of US devices in modern anesthetic practice, newer regional techniques based on detailed knowledge of innervations of the breast have been developed such as the Pecs blocks I and II and SPB, which were first described by Blanco et al. , and erector spinae plane block, which was first described by Forero et al. .
To prolong the duration of the analgesia of SBP, dexmedetomidine was added to levobupivacaine. Multiple theories have been proposed to clarify the prolonged analgesic effect of adding dexmedetomidine to perineural LA beside its central action after systemic absorption. The first one is vasoconstriction mediated by action of vascular α2 adrenoceptor at injection site, which delays the absorption of LA and prolongs its efficacy. It also enhances the local release of encephalins .
The second theory is a direct effect on peripheral nerve activity, which is mediated directly by blocking an activity-dependent cation current (the Ih current); the Ih current normally acts to reset the nerve from a hyperpolarized state back to the resting membrane potential . By keeping the nerve in a hyperpolarized state, the nerve is unable to generate a new action potential, especially in C-fibers and Aδ fibers .
The group that received a combination of levobupivacaine and dexmedetomidine (D group) had a significantly longer duration till the time of first analgesia request compared with L and C groups correspondingly (618±126 vs. 444±72 vs. 21.6±6.6 min; P<0.001) and significantly lower total 24-h pethidine consumption (60±12 vs. 85±17 vs. 150±16 mg; P<0.001).
In agreement with these results, Manzoor et al.  demonstrated that addition of dexmedetomidine to bupivacaine (30 ml of 0.25%) in Pecs II significantly prolonged the duration of postoperative analgesia by ∼40% compared with the use of bupivacaine alone (1024.0±124.9 vs. 726.4±155.3 min; P<0.001). The more prolonged effect than this study’s results may be attributed to the fact they used dexmedetomidine in dose of 1 µg/kg compared with 0.5 µg/kg in this study.
Abdelaal et al.  showed that the addition of dexmedetomidine (100 µg) to levobupivacaine (20 ml of 0.375%) in transverse abdominis plane block after abdominoplasty delayed the time to the first analgesia request compared with levobupivacaine alone (205±10.2 vs. 181±12.6 min; P<0.001) and also decreased total 24-h pethidine consumption (136±13.4 vs. 172±15.8 mg; P<0.001).
Mazy et al.  showed that dexmedetomidine (1.0 µg/kg) added to preperitoneal bupivacaine (bolus 20 ml of 0.7 mg/kg via surgically inserted catheter) after elective cesarean section significantly delayed time to the first analgesia request compared with dexamethasone (8.0 mg) and lowered Numerical Rating Scale from 6 to 24 h postoperatively. Total nalbuphine consumption was comparable between both groups.
This study demonstrated that VAS scores at rest and at arm abduction were significantly lower during 1 h stay in PACU and at 2, 4, 6 h in D and L groups in comparison with C group. No significant difference in VAS scores between D and L groups during 1 h stay in PACU and till 6 h postoperatively could be detected. Meanwhile, VAS scores were significantly lower at 8 and 12 h postoperatively in D group compared with L group owing to the extended analgesic effect of dexmedetomidine up to 12 h.
In agreement with these results, Matsumoto et al.  reported significantly lower VAS scores in the PACU and at 24 h after MRM in GA with SPB+Pecs I group compared with GA only group.
In the study done by Hetta and Rezk  comparing SPB and thoracic paravertebral block in MRM, VAS scores at rest and motion were comparable at 0, 2, 4, and 6 h postoperatively and were higher in SPB group at 8, 16, and 24 h postoperatively.
In contrast to these results, Rahimzadeh et al.  found no significant difference in VAS scores at all measurement intervals between GA–SPB–PCA group and GA–PCA group. This was on the expense of much higher PCA fentanyl consumption and much earlier need of PCA fentanyl request in GA–PCA group. This insignificant difference in VAS can be attributed to the use of PCA for better pain management and higher patient satisfaction. Moreover, VAS was assessed at rest only not with motion also.MAP and HR were significantly lower in D group in comparison with L group from 15 min after SPB up to 8 h postoperatively (P<0.001), but it was not clinically significant; none of the patients in D group required ephedrine or had bradycardia that required atropine. This can be explained by the low dose (0.5 µg/kg) of dexmedetomidine used in the block.
Dexmedetomidine can cause hypotension and bradycardia particularly at higher doses owing to postsynaptic activation of the inhibitory α2 adrenoceptors in the medullary vasomotor center, which leads to a reduction in norepinephrine release and central sympathetic outflow. Bradycardia is caused by an increase in the vagal tone resulting from central stimulation of parasympathetic outflow, as well as a reduced sympathetic drive .
Mohamed et al.  observed that addition of dexmedetomidine 1 µg/kg to bupivacaine in thoracic paravertebral block in patients undergoing MRM prolonged the duration of analgesia and reduced analgesic requirements with no serious hemodynamic adverse effects.
In this study, patient satisfaction scores in D group were significantly higher compared with L and C groups. Meanwhile, patient satisfaction scores in L group were significantly higher compared with C group.
Aksu et al.  showed that addition of dexmedetomidine 1 µg/kg to bupivacaine on transverse abdominis plane block increased satisfaction score for patients undergoing lower abdominal surgery compared with GA only and bupivacaine only groups.
PONV was significantly higher in C and L groups in comparison with D group. This may be owing to the use of more postoperative opioids in C and L groups than in D group. Owing to performance of the block under US visualization, block-related complications such as pneumothorax, vascular injection, or LA toxicity did not occur.
The limitations of this study include that different doses of dexmedetomidine were not used; a lower dose of dexmedetomidine could produce the same analgesic effect with least adverse effects. Another limitation of this study was the lack of proper assessment of success rate of SPB procedure using sensory loss to pinprick as it was performed following the induction of GA, but we relied upon the use of ultrasonography-guided block for proper placement of blocking needle. A third limitation was the inability to assess dexmedetomidine plasma concentrations among study patients to determine whether its action was related to systemic absorption or pure local effect.
| Conclusion|| |
The addition of dexmedetomidine to levobupivacaine in US-guided serratus plain block during MRM surgery prolongs the postoperative analgesia, delays time of first analgesia request, reduces postoperative opioid consumption, and reduces PONV owing to lower total opioid consumption compared with levobupivacaine alone.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]