Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 9  |  Issue : 2  |  Page : 296-303

Shoulder block versus interscalene block for postoperative pain relief after shoulder arthroscopy


Department of Anesthesia and Intensive Care, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Date of Submission05-Sep-2015
Date of Acceptance20-Nov-2015
Date of Web Publication11-May-2016

Correspondence Address:
Hala E Zanfaly
Department of Anesthesia and Intensive Care, Faculty of Medicine, Zagazig University, Zagazig
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-7934.182272

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  Abstract 

Background
Adequate pain control allows early rehabilitation and improves outcome after shoulder arthroscopic procedures.
Objective
The aim of this study was to compare the interscalene nerve block (ISB) with shoulder block (ShB) (suprascapular and axillary nerve blocks) for postoperative pain relief after arthroscopic shoulder surgery.
Design
This was a prospective, randomized, comparative study.
Patients and methods
A total of 75 patients of ASA grade I or II scheduled for shoulder arthroscopic surgery were equally divided into three groups (25 patients each): the general anesthesia (GA)-only group; the GA with ISB group; and the GA with ShB group. The nerve block was guided by both ultrasound and nerve stimulator. Visual analogue scale score was evaluated at the recovery room and 2, 4, 8, 16, and 24 h postoperatively. The time to first call for analgesia, total analgesic requirement for 24 h postoperatively, patient satisfaction, and any complications were recorded.
Results
The visual analogue scale score was significantly less in the GA + ISB and GA + ShB groups compared with the GA-only group (P < 0.001). The time to first analgesic request was significantly longer in the GA + ISB group [10 (9-10 h)] and GA + ShB group [9 (9-10 h)] compared with the GA-only group [1 (1 h)] (P < 0.001). The total dose of morphine consumption was significantly higher in the GA-only group [10 (9-10 mg)] compared with the GA + ISB group [6 (5-6 mg)] and the GA + ShB group [6 (6-7 mg)] (P < 0.001). Patient satisfaction was significantly higher in the GA + ISB group [9 (9-10)] and in the GA + ShB group [8 (8-9)] compared with the GA-only group [1 (1-2)] (P < 0.001). The incidence of complications was significantly higher in the GA + ISB group compared with the other two groups (P < 0.001).
Conclusion
ShB was as effective as ISB for postoperative pain relief but with fewer complications. Thus, ShB is a good alternative for patients at high risk for adverse events with ISB.

Keywords: interscalene block, shoulder arthroscopy, shoulder block


How to cite this article:
Zanfaly HE, Aly AA. Shoulder block versus interscalene block for postoperative pain relief after shoulder arthroscopy. Ain-Shams J Anaesthesiol 2016;9:296-303

How to cite this URL:
Zanfaly HE, Aly AA. Shoulder block versus interscalene block for postoperative pain relief after shoulder arthroscopy. Ain-Shams J Anaesthesiol [serial online] 2016 [cited 2021 Oct 25];9:296-303. Available from: http://www.asja.eg.net/text.asp?2016/9/2/296/182272


  Introduction Top


Shoulder arthroscopy can effectively treat a number of injuries and diseases of the shoulder on an ambulatory basis [1,2].

Although shoulder arthroscopy is considered minimally invasive, it is associated with severe intraoperative and postoperative pain. Hence, it requires adequate analgesia and muscle relaxation for the procedure. For shoulder arthroscopy, regional anesthesia is better than general anesthesia (GA) because of the extended postoperative analgesia and rapid recovery towards discharge [3-5].

Furthermore, GA with a regional nerve block reduces intraoperative anesthetic requirements resulting in rapid recovery and reduction of postoperative pain [6].

Interscalene brachial plexus block may be the most reliable and most frequently used regional block technique for shoulder surgery; however, it has the potential for many complications. The most common of these complications is phrenic nerve palsy, which is reversible but may result in significant respiratory distress especially in patients with compromised respiratory function. Other less common yet serious complications include Horner's syndrome, recurrent laryngeal nerve block that may result in hoarseness of voice, vascular puncture, brachial plexus neuropathy, and unintended injection of local anesthetic into the subarachnoid space, epidural space, or vertebral artery [7-9].

Interscalene block (ISB) also produces intense motor block of the shoulder, which may extend to the hand, predisposing the patient to injuries, and thus more distal block may be more appropriate and safe [9,10].

On the basis of the fact that ISB provides anesthesia for the shoulder joint by blocking C5 and C6 nerve roots and most of the nerve supply to the shoulder from these two nerve roots are carried by two nerves - namely, the suprascapular and the axillary nerves - the shoulder block (ShB) that involves the combined block of these two specific nerves was proposed to provide anesthesia and postoperative analgesia for the shoulder surgery as a safe alternative to ISB [11].

The suprascapular nerve supplies sensation for most of the posterior, medial, and superior part of the shoulder joint capsule. It also supplies the supraspinatous and infraspinatous muscles of the rotator cuff and some branches to the teres minor, the glenoid, acromion, and the posterior surface of the scapula [10].

The anterior, lateral, and inferior structures of the shoulder joint are supplied by the axillary nerve, which also supplies the deltoid muscle and gives some fibers to the teres minor. The axillary nerve also supplies the skin overlying the deltoid muscle [12]. The use of ultrasound and nerve stimulator in performing both blocks provided better visualization and localization of the nerves, resulting in successful blockade with fewer complications [13-15].

The hypothesis of this study was that the specific blockade of the suprascapular and axillary nerves (ShB) using ultrasound guidance with nerve stimulation for the block may be as effective as ISB for postoperative pain relief after shoulder arthroscopy, but with fewer side effects. In previous studies, ShB by selective blockade of suprascapular and axillary nerves was reported to be a safe and effective technique for intraoperative anesthesia and postoperative analgesia for shoulder arthroscopy [10,11]. Compared with ISB, ShB provides satisfactory analgesia like ISB with the advantage of minimal complications and motor block restricted to the shoulder [12].

The aim of this study was to compare ISB with the selective blockade of suprascapular and axillary nerves (ShB) for postoperative pain relief after shoulder arthroscopic surgery using ultrasound and nerve stimulator as guidance.


  Patients and methods Top


After obtaining approval from the local Ethics committee and written informed consent from each patient, this prospective randomized comparative study was carried out at the Anesthesia Department of Zagazig University Hospital from November 2012 to July 2014.

A total of 75 patients of both sexes of ASA class I or II aged between 25 and 55 years undergoing arthroscopic shoulder procedures (subacromial decompression, rotator cuff repair not involving the subscapularis muscle, recurrent shoulder dislocation, frozen shoulder) were enrolled in this study.

Patients were excluded from the study if they had undergone previous surgery in the same shoulder, had a history of psychiatric disorder, had a BMI greater than 35 kg/m 2 , had chronic lung diseases, were on chronic analgesic therapy, or had contraindications to regional nerve block. The patients were randomly allocated into three equal groups (each of 25 patients) using sealed opaque numbered envelopes:

  • GA-only group: this group consisted of patients who received GA only
  • GA + ISB group: this group consisted of patients who received ultrasound and nerve stimulator-guided ISB before induction of GA
  • GA + ShB group: this group consisted of patients who received ultrasound and nerve stimulator-guided suprascapular and axillary nerve blocks (ShB) before induction of GA.
For each patient, an 18-G intravenous cannula was applied to a peripheral vein in the forearm opposite the surgical side, and Ringer lactate solution was given. All patients were premedicated using midazolam 0.03 mg/kg intravenously. Standard monitors were attached in the form of five-lead ECG, noninvasive blood pressure monitor, pulse oximeter, and capnograph. The patients were instructed preoperatively to use visual analogue scale (VAS) for pain.

The ISB and ShB were performed before induction of GA guided by ultrasound (SIEMENS Acuson, SC 2000; Siemens Medical Solutions, USA, Made in Korea) and nerve stimulator (B-Braun-Stimuplex HNS 11-12218, Stockert GmbH, Botzinger StraBe 72, D-79111 Freiburg, Germany).

The technique of interscalene nerve block [6, 16, 17]

The patients were positioned supine with the head turned away from the side to be blocked and the neck slightly extended. The skin of the neck was sterilized and the ultrasound probe was placed in a sterile sheath. This study used a linear probe of 7-13 MHz frequency and the depth was set to 2-4 cm. The probe was first placed at the level of the cricoid cartilage over the sternomastoid muscle and first moved laterally to identify the carotid artery and the jugular vein and then laterally and posteriorly until visualization of the brachial plexus as hypoechoic nerve structure between the anterior and middle scalene muscle. Confirmation of absence of vascular structure was made by color Doppler. After skin infiltration with 2 ml of lidocaine 1% a 22-G, 5-cm nerve block needle (B. Braun Medical Inc., Bethlehem, Pennsylvania, USA) (connected to nerve stimulator) was inserted in plane with the probe to visualize the entire needle length. When the needle tip was seen close to the brachial plexus roots, a current less than 0.5 mA produces contraction of the triceps muscle (right position), an assistant started to inject the local anesthetic (25-30 ml 0.5% bupivacaine) with aspiration every 5 ml to avoid intravascular injection and the local anesthetic spread was observed. Block success was assessed every 5 min from the end of local anesthetic injection until readiness for surgery.

Sensory block was assessed by pinprick using 22-G needles over the lateral side of the forearm and thumb. Motor block was assessed by asking the patient to abduct the arm at the shoulder and flex the forearm at the elbow against resistance. The block was considered a failure if the block was not successful 30 min after injection of the local anesthetic.

The technique of shoulder block (suprascapular and axillary nerve blocks) [10,11]

Suprascapular nerve block [18-20] was performed with the patient sitting and his arm flexed at the elbow and resting on his anterior thigh. After skin sterilization, a linear ultrasound probe (7-13 MHz frequency) was placed in a sagittal plane at the superior medial border of the scapula. The probe was moved laterally and then placed parallel to the scapular spine. It was then tilted cephaled to identify the scapular fossa where the supraspinatus muscle and the bony fossa under it can be visualized. Then by moving the transducer slowly laterally, the suprascapular notch can be identified where the suprascapular nerve can be seen as a round hypoechoic structure about 4 cm in depth behind the transverse scapular ligament. Two milliliters of 1% lidocaine was used to anesthetize the skin, and then a 22-G 10-cm nerve block needle (B. Braun Medical Inc.) (connected to a peripheral nerve stimulator) was inserted in plane with the ultrasound probe. When the needle tip was seen in the suprascapular notch and after confirmation of absence of vascular structure by color Doppler, a current less than 0.5 mA produces contraction of deltoid muscle or supraspinatous and infraspinatous muscles, 7-10 ml of 0.5% bupivacaine was injected with aspiration every 3 ml to avoid intravascular injection and the spread of the local anesthetic was observed [Figure 1].
Figure 1: Anatomy: (1) supraspinatus muscle, (2) spine of scapula, (3) deltoid muscle, (4) suprascapular artery, (5) suprascapular nerve,(6) teres minor muscle, (7) infraspinatus muscle, (8) teres major muscle, (9)
latissimus dorsi muscle, (3) axillary nerve


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Axillary nerve block [10, 22, 23]: this was performed while the patient was still in the sitting position with the shoulder adducted and internal rotation at 45°, the elbow flexed at 90° and the hand resting on the knee. The probe was placed parallel to the shaft of the humerus and about 2 cm below the posterolateral part of the acromion on the dorsal side of the arm. The surgical neck of the humerus was identified, and then a short-axis view of the circumflex artery (which is the most reliable land mark) was visualized. The axillary nerve is located just cranial to the circumflex artery in the neurovascular space between the teres minor muscle superiorly, the deltoid muscle posteriorly, the triceps muscle caudally, and the shaft of the humerus anteriorly. A 22-G 10-cm nerve block needle (B. Braun Medical Inc.) (attached to a nerve stimulator) was inserted in line with the ultrasound probe from its cranial end to place the needle tip just cranial to the circumflex artery under the muscle fascia. A current less than 0.5 mA produces twitches of the deltoid muscle. Then 7-10 ml of 0.5% bupivacaine was injected slowly while aspirating every 3 ml to avoid intravascular injection [Figure 1].

Sensory block was assessed by pinprick using a 22-G needle over the skin covering the distal part of the deltoid muscle. The motor block was assessed by evaluating the deltoid muscle function: the anterior part of the deltoid was assessed by active resistance against posterior and downward movement of the arm, whereas the shoulder is 70° abducted and the elbow is flexed 30°. The middle part of the deltoid was assessed by active resistance against adduction of the shoulder while it is in 90° abduction and the elbow is at 90° flexion. The posterior part of the deltoid was assessed by active resistance against flexion of the arm with shoulder at 30° extension and the elbow at 90° flexion.

The assessment of the blocks was done every 5 min from the end of local anesthetic injection until readiness for surgery. If the block was not effective after 30 min from local anesthetic injection, it was considered unsuccessful.

After the blockade, all patients received GA using atropine 0.01 mg/kg, propofol 2.0-2.5 mg/kg, fentanyl 1 mg/kg, and atracurium 0.5 mg/kg for insertion of endotracheal tube, and controlled ventilation was started.

Anesthesia was maintained with oxygen, isoflurane (1-2%), and 0.1 mg/kg atracurium to maintain blood pressure and heart rate within the normal range (not exceeding 20% of the baseline value). Supplementary doses of fentanyl 0.5 mg/kg intravenously were given until 10 min before the end of surgery.

At the end of surgery, anesthesia was stopped and neuromuscular blockade was reversed with 0.05 mg/kg neostigmine and 0.01 mg/kg atropine.

Postoperative analgesia was provided according to the local protocol with diclofenac natrium (voltaren) intramuscularly every 8 h, with the first dose administered before the end of the procedure. If VAS score for pain was greater than 3, morphine 0.1 mg/kg intramuscularly was given to the patient as rescue analgesia.

Data collection

  1. Age, weight, sex, and duration and type of surgery were recorded
  2. VAS score from 0 = no pain to 10 = worst pain was used to assess the postoperative pain at rest and on passive movement at the following times: in the recovery room and 2, 4, 8, 16, and 24 h postoperatively
  3. The time to first analgesic request was recorded. It was defined as the time from recovery until VAS score greater than 3
  4. The total dose of intravenous morphine used over 24 h postoperatively was recorded
  5. Patient satisfaction: the following day after the operation the patients were evaluated with a questionnaire on a 10-point scale to assess the patient satisfaction about the procedure 24 h postoperatively (from 0 = not satisfied to 10 = fully satisfied) [11,12]
  6. Any complications during and after the performance of the block - for example, pneumothorax, Horner's syndrome, hoarseness, difficulty in breathing, weakness, and paresthesia in the arm - were recorded
  7. Also, postoperative nausea and vomiting were recorded.
Sample size

The total mean morphine consumption in the ShB group was 8.4 ± 4.9 mg, whereas that in the GA group was 12.3 ± 4.6 mg at 80% power and 95% confidence interval. The estimated sample was 25 in each group (open Epi).

Statistical analysis

Data were checked, entered, and analyzed using SPSS, version 20. Data were expressed as mean ± SD or median (interquartile range) for quantitative variable and as number and percentage for categorical variables. The c2 -test, analysis of variance (F-test), and least significant difference tests were used when appropriate. P value less than 0.05 was considered statistically significant.


  Results Top


The demographic data and duration and type of surgery were comparable between the three groups (P > 0.05) [Table 1].
Table 1 Demographic data of patients and duration and type of surgery

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The VAS score during rest and passive movement was significantly less in the GA + ISB and GA + ShB groups in the recovery room and 2, 4, 8, and at 16 h postoperatively when compared with the GA-only group (P < 0.001) [Table 2].
Table 2 Visual analogue scale during rest and passive movement at different times of the study

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VAS score during rest in the recovery room and 2, 4, 8, and 16 h postoperatively for the GA + ISB group was 0, 0, 0, 4 (4), and 4 (3.5-5), respectively, that for the GA + ShB group was 0, 0, 0, 4 (4-5), and 4 (4-5), respectively, and that for the GA-only group was 3 (2-3), 4 (3-5), 4 (4-5), 6 (6-7), and 6 (6-7), respectively [Table 2].

VAS score during passive movement in the recovery room and 2, 4, 8, and 16 h postoperatively for the GA + ISB group was 0, 0, 2 (2-3), 4 (3.5-5), and 5 (5-6), respectively, that for the GA + ShB group was 0, 0, 3 (2-4), 4 (3-4), and 5 (5-6), respectively, and that for the GA-only group was 3 (3-4), 4 (3.5-5), 5 (5-6), 6 (6-7), and 7 (6-8), respectively [Table 2].

At 24 h postoperatively, there were no significant differences between the three studied groups in VAS score at rest and during passive movement (P > 0.05) [Table 2].

VAS score during rest and passive movement at 24 h postoperatively for the GA + ISB group was 6 (6-7) and 6 (6-7), respectively, that for the GA + ShB group was 6 (6-7) and 6 (5-7), respectively, and that for the GA-only group was 7 (6.5-8) and 7 (7-8), respectively [Table 2].

Of note, there was no significant difference in VAS score at rest and during passive movement in all the studied times between GA + ISB and GA + ShB groups (P > 0.05) [Table 2].

As regards the time to first analgesic request, it was significantly longer in the GA + ISB group [10 (9-10 h)] and GA + ShB group [9 (9-10 h)] when compared with the GA-only group [1 (1 h)] (P < 0.001) [Table 3].
Table 3 The time to first analgesic request, morphine consumption, and patient satisfaction in the studied groups

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The total mean morphine consumption over 24 h postoperatively was significantly higher in the GA-only group [10 (9-10 mg)] compared with the GA + ISB group [6 (5-6 mg)] and GA + ShB group [6 (6-7 mg)] (P < 0.001) [Table 3].

Patient satisfaction was significantly better in the GA + ISB group [9 (9-10)] and GA + ShB group [8 (8-9)] compared with the GA-only group [1 (1-2)] (P < 0.001) [Table 3]. There were no significant differences between the GA + ISB group and GA + ShB group as regards the time to first analgesic request, the total dose of morphine consumption over 24 h postoperatively, and patient satisfaction (P > 0.05) [Table 3].

The GA + ShB group had the lowest incidence of complications compared with the other two groups. In the GA + ISB group there were some complications like Horner's syndrome, which appeared with the onset of the block in nine patients (36%), and seven other patients (28%) developed weakness in the arm postoperatively. The difference was significant when compared with the other two groups (P < 0.001) [Table 4]. The patients were instructed about the occurrence of Horner's syndrome and reassured about its benign nature and that it will disappear with time without any sequelae. The patients who reported weakness in the arm underwent clinical examination and assessment.
Table 4 Complications in the studied groups

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Nausea was significantly high in the GA-only group (10 patients, 40%) compared with the other two groups (one patient in each of the other two groups) (P < 0.001) [Table 4]. No patient in the three groups developed pneumothorax [Table 4].

Other short-term complications like hoarseness, difficulty in breathing, paresthesia in the arm, and vomiting were comparable between the three groups (P > 0.05) [Table 4]. Paresthesia in the arm occurred during stimulation. The direction of the needle was changed and the procedure continued smoothly. Hoarseness of voice and difficulty in breathing started shortly after administration of the local anesthesia. Vomiting in all patients was not frequent and was self-limited [Figure 2] and [Figure 3].
Figure 2: Visual analogue scale during rest at different times in the studied groups. Values are mean ± SD. VASR, visual analogue scale at rest. **P < 0.001 compared with the other groups

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Figure 3: Visual analogue scale during passive movement at different times in the studied groups. Values are mean ± SD. VASM, visual analogue scale at passive movement. **P < 0.001 compared with the other groups

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  Discussion Top


Arthroscopic shoulder procedures have ?#948;30-70% incidence of severe intraoperative and postoperative pain, which interferes with the initial recovery and rehabilitation [20,24].

Although ISB has been considered one of the most reliable and effective methods for intraoperative and postoperative analgesia during arthroscopic shoulder surgery, it is associated with significant complications [3, 25, 26].

The present study used suprascapular and axillary nerve blockade (ShB) as an alternative to ISB and found that it was safe and effective in producing postoperative analgesia with minimal complications . Also, using combined ultrasound and nerve stimulator as guidance for the blockade facilitates the direct visualization and localization of the neural structure, which allows better local anesthesia disposition around the roots of the plexus and the peripheral nerves, thus improving the success of block performance and reducing the complications of each blockade [27-29].

This study showed significantly lower VAS scores at rest and on passive movement in GA + ISB and GA + ShB groups up to 16 h postoperatively compared with the GA-only group. These results were in agreement with the results of Checcucci et al. [11], who reported a low VAS score during the first 24 h after ShB. Also, Price [10] found that the combination of suprascapular and axillary nerve blockade provided complete shoulder joint analgesia. The analgesic effect achieved by single injection or continuous infusion ISB was proved by many studies [6,30-32] . In this study, postoperative pain assessment showed high VAS score [6,7] at 8, 16, and 24 h postoperatively. We dealt with any increase of VAS immediately and properly with rescue drug (morphine 0.1 mg/kg intramuscularly). The explanation for the high VAS scores was that the severe pain was a sudden and not a gradual one as most of the patients felt severe pain suddenly. Once the score was recorded, it took a few seconds to attenuate it by giving the rescue analgesic to the patients immediately.

The time to first analgesic request was significantly longer in the GA + ISB and GA + ShB groups compared with the GA-only group. This leads to a significant decrease in morphine consumption over the first 24 h postoperatively in the GA + ISB and GA + ShB groups compared with the GA-only group.

These results were in accordance with the results of Price [10], who found that shoulder blockade causes pain relief similar to ISB with low morphine consumption postoperatively.

The present study showed a good level of patient satisfaction in the GA + ISB and GA + ShB groups compared with the GA-only group.

Checcucci et al. [11] reported that augmentation of suprascapular nerve block with axillary nerve block produced a high level of patient satisfaction.

The low patient satisfaction in the GA-only group may be due to early sensation of pain and the higher incidence of postoperative nausea and vomiting, which results from the severity of pain and the increased postoperative use of analgesics. In contrast, the GA + ISB and GA + ShB groups showed a lower incidence of postoperative nausea and vomiting in comparison with the GA-only group. These results were in accordance with the results of Al-Kaisy et al. [33] and Laurila et al. [34].

Interestingly, the GA + ShB group in this study showed minimal complications during and after block performance compared with the GA + ISB group. These results were confirmed by several previous studies [10, 12, 31].

Also, Barber [20], Checcucci et al. [11], and Feigi et al. [35] demonstrated that there were no complications with shoulder blockade during the block performance, such as pneumothorax, suprascapular nerve injury, and hematoma.

In the present study, Horner's syndrome and weakness in the upper limb were the most common complications in the GA + ISB group, whereas other complications were few and temporary. Singelyn et al. [36] reported Horner's syndrome and hoarseness as complications in ISB. Other studies [31,37] found that extensive paralysis of the muscles of the upper limb was considered a sign of effective ISB, but it causes discomfort to the patient.

In contrast, other potential serious complications associated with ISB were recorded in previous studies [38,39]: for example, inadvertent epidural and spinal anesthesia, vertebral artery injection, paralysis of the vagus, recurrent laryngeal and cervical sympathetic nerve, and injury to the brachial plexus. Also, Urmey [40] and Pere [41] recorded phrenic nerve block in all patients undergoing ISB. The higher incidence of the potentially serious complications in the previous studies may be due to unpredictable spread of local anesthetic to important adjacent neural structures such as phrenic and vagus nerves and the stellate ganglion [37,40].

The lower rate of complications in the GA + ISB and GA + ShB groups in the present study compared with previous studies [37-40] may be due to the use of a combination of ultrasound and neurostimulation as guidance, which facilitated the identification in all patients within a short time, improved block quality, and allowed the avoidance of intraneuronal or intravascular injection. These results were in accordance with those of other previous studies [14, 28, 42].

Finally, in the present study both ISB and ShB provided similar postoperative analgesia, but the high rate of complications in ISB made the ShB superior for use in arthroscopic shoulder surgery especially in patients with pulmonary diseases.

This study had some limitations:

  1. The first limitation is that only a small number of patients were enrolled
  2. Second, GA was used as a baseline in all groups, which likely biased the anesthetic effects of the nerve block. Also this study did not measure the cortisol level intraoperatively to assess the stress response and the analgesic effect of the block, which can be studied in other research.

  Conclusion Top


ShB (suprascapular and axillary nerve blocks) was as effective as ISB for postoperative pain relief after arthroscopic shoulder surgery, but with fewer complications. Thus, ShB is a good alternative for patients at high risk for adverse events with ISB.

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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