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ORIGINAL ARTICLE
Year : 2020  |  Volume : 68  |  Issue : 3  |  Page : 617--623

Effect of Stellate Ganglion Block on Intraoperative Propofol and Fentanyl Consumption in Patients with Complex Regional Pain Syndrome Undergoing Surgical Repair of Brachial Plexus Injury: A Randomized, Double-blind, Placebo-controlled Trial

Vanitha Rajagopalan1, Rajendra Singh Chouhan1, Mihir Prakash Pandia1, Ritesh Lamsal2, Parmod Kumar Bithal3, Girija Prasad Rath1,  
1 Department of Neuroanaesthesiology and Critical Care, All India Institute of Medical Sciences, New Delhi, India
2 Department of Anaesthesia and Intensive Care, National Academy of Medical Sciences, Kathmandu, Nepal
3 Department of Anesthesia, King Fahad Medical City, Riyadh, Saudi Arabia

Correspondence Address:
Dr. Girija Prasad Rath
Department of Neuroanaesthesiology and Critical Care, Neurosciences Centre, All India Institute of Medical Sciences, New Delhi - 110 029
India

Abstract

Introduction: Stellate ganglion block (SGB) is commonly performed to treat chronic painful conditions, such as complex regional pain syndrome (CRPS) and postherpetic neuralgia. However, whether it is effective in reducing anesthesia and analgesia requirement during surgery (acute pain) is not known. Materials and Methods: Sixty American Society of Anesthesiologists (ASA) physical status I and II patients with CRPS type II undergoing surgery for repair of brachial plexus injury were randomized (1:1) to receive SGB with either 10 mL of 0.5% bupivacaine (Group B) or a matching placebo (Group S) before induction of anesthesia. Results: There was a significant reduction in the requirement of total intraoperative propofol (1659.7 ± 787.5 vs. 2500.7 ± 740.9 mg, P = 0.0003) and fentanyl (190.0 ± 82.5 vs. 327.3 ± 139.3, P = 0.0001) in Group B compared with Group S. Similarly, in Group B, the time to first analgesic was much longer (328 ± 219 vs. 64 ± 116 min, P = 0.000) and postoperative fentanyl requirement for 24 h was lesser compared to Group S (0.6 ± 1.1 vs. 2.1 ± 1.3 μg/kg, P = 0.000). Conclusion: SGB is effective in reducing the requirement of intraoperative propofol and fentanyl as well as decreasing opioid requirement in the postoperative period in patients with CRPS type II undergoing surgery.



How to cite this article:
Rajagopalan V, Chouhan RS, Pandia MP, Lamsal R, Bithal PK, Rath GP. Effect of Stellate Ganglion Block on Intraoperative Propofol and Fentanyl Consumption in Patients with Complex Regional Pain Syndrome Undergoing Surgical Repair of Brachial Plexus Injury: A Randomized, Double-blind, Placebo-controlled Trial.Neurol India 2020;68:617-623


How to cite this URL:
Rajagopalan V, Chouhan RS, Pandia MP, Lamsal R, Bithal PK, Rath GP. Effect of Stellate Ganglion Block on Intraoperative Propofol and Fentanyl Consumption in Patients with Complex Regional Pain Syndrome Undergoing Surgical Repair of Brachial Plexus Injury: A Randomized, Double-blind, Placebo-controlled Trial. Neurol India [serial online] 2020 [cited 2020 Sep 23 ];68:617-623
Available from: http://www.neurologyindia.com/text.asp?2020/68/3/617/288992


Full Text



Complex regional pain syndrome (CRPS) is defined as chronic, severe pain in the limbs with neuropathic characteristics that may present with sensory, autonomic, motor, and trophic impairments.[1] CRPS type I has no direct evidence of nerve injury in the affected limb, whereas, CPRS type II (CRPS II) has distinct evidence of direct nerve injury.[2]

The stellate ganglion is formed by the fusion of the inferior cervical ganglion with the first thoracic ganglion and supplies sympathetic fibers to the head, neck, and upper limb. The contribution of sympathetic overflow or hyperactivity to the pathogenesis of chronic pain has been extensively studied.[3],[4],[5] Stellate ganglion block (SGB) is widely practiced for the management of chronic pain even though there is paucity of controlled studies validating its efficacy.[6],[7],[8],[9],[10] However, the use of SGB to treat acute nociceptive pain has been reported very sparingly.[11],[12],[13] In general, nociceptive events during neurosurgical anesthesia that produce painful stimuli such as skull-pin fixation, dural incision, and tunneling phase of ventriculo-peritoneal shunt surgery are treated with supplemental analgesics or deepening the plane of anesthesia. Therefore, we planned to study the effect of SGB on intraoperative propofol and fentanyl requirement in patients with CRPS II presenting for surgical repair of brachial plexus injury (BPI). The secondary objectives were to study the effect of SGB on postoperative analgesia requirement and perioperative complications in these patients. SGB has been found to reduce the requirement of postoperative analgesia,[14],[15] but there is no previous study that has examined its effect on the requirement of intraoperative anesthetics and analgesics.

 Materials and Methods



Study design, randomization, and blinding

After approval from the Institute Ethics Committee, a double-blind, randomized controlled trial was conducted to compare the effect SGB on intraoperative propofol and fentanyl consumption in patients with CRPS II undergoing surgical repair of BPI. The patients were randomized (1:1) into two groups - bupivacaine (Group B) and saline (Group S) based on computer-generated randomization numbers. The study drug was prepared and SGB performed as per group allocation by an anesthesiologist who was not involved in patient management. In both groups, a 10-mL sterile syringe was filled with either bupivacaine (0.5%) or normal saline as per randomization, and labelled as “Test Drug” for the purpose of blinding the attending anesthesiologist and other personnel in the operating room (OR). The senior anesthesiologist who performed the block then recorded the presence or absence of ptosis, miosis, enophthalmos, conjuctival congestion, and vasodilation of the upper limb. The anesthesiologist who managed the case was unaware of the drug given and its effect. The patient was also unaware to which group he or she belonged to.

Sample size calculation and patient selection

Assuming a 5% difference in the mean propofol consumption between the two groups, with an α error of 0.5, a total of 27 subjects were required in each group to achieve a power of 90%. So, we decided to include 60 consecutive patients in this study. Inclusion criteria were patients of American Society of Anesthesiologists (ASA) physical status 1 and 2, of either sex, between the ages of 18 and 65 years with CRPS II undergoing surgical repair of BPI. Exclusion criteria were pregnancy, major hepatic or renal diseases, allergy to local anesthetics, patients on anticoagulants, and those who were previously treated with SGB. Written informed consent was obtained from all eligible patients. Visual analog scale (VAS) score was explained to all the patients to assess the severity of pain. Routine medications were continued as per institutional practice.

Stellate ganglion block

In the OR, standard anesthesia monitors including pulse oximetry, electrocardiography, noninvasive blood pressure and skin temperature probe on the affected limb were attached and preoperative VAS score was noted. With the patient in supine position and neck slightly extended with a pillow under the shoulders, ipsilateral SGB was performed using landmark technique (modified anterior paratracheal approach), as described by Carron and Litwiller.[16] After antiseptic preparation of the area with betadine solution, skin and subcutaneous tissue were pressed firmly onto the Chassaignac's tubercle (transverse process of sixth cervical vertebra) between the trachea and the carotid sheath at the level of cricoid cartilage. After pushing the sternocleidomastoid muscle and carotid artery laterally, a 22-G, 5-cm sterile needle was introduced vertically downwards to meet the C6 vertebra. When bone was hit, the needle was walked laterally till bony resistance disappeared and then it was withdrawn by 1–2 mm. After negative aspiration for blood, CSF or air, 10 mL “Test Drug” was injected slowly. All patients were monitored for 10 min for the development of features of ipsilateral sympatholysis. The anesthesiologist who performed the block then recorded the presence or absence of ptosis, miosis, enophthalmos, conjunctival congestion, and vasodilation of the upper limb. Heart rate (HR), mean blood pressure (MAP), VAS score, and temperature of the affected limb were also continually recorded.

Anesthetic management and postoperative care

Before induction of anesthesia, a sensor strip for bispectral index (BIS) monitoring was secured on the patient's forehead. Intravenous (IV) propofol was used for induction of anesthesia and fentanyl (2 μg/kg) was used for analgesia. A proseal laryngeal mask airway (PLMA) of appropriate size was inserted under adequate anesthetic depth. Anesthesia was maintained with 60% nitrous oxide in oxygen, propofol infusion and intermittent boluses of fentanyl (0.5 μg/kg). Muscle relaxants were avoided to facilitate neuro-monitoring. Mechanical ventilation was adjusted to maintain an end-tidal carbon dioxide (EtCO2) of 35–40 mm Hg. Propofol infusion was started at the rate of 10 mg/kg/h and titrated to a BIS value of 50 ± 5. HR and MAP were maintained within 20% of their respective baseline values. If BIS increased beyond 55, a bolus of propofol (0.5 mg/kg) was administered, and the propofol infusion rate was increased by 5 mL/h; this procedure was repeated till BIS stabilized in the range of 50 ± 5. If HR or MAP increased beyond 20% from baseline, and BIS was less than 55, a bolus of fentanyl bolus (0.5 μg/kg) was administered and repeated every 10 mins until the hemodynamic parameters returned back to 20% of baseline values. Forced air warming blankets and warm IV fluids were used to maintain normothermia. Significant intraoperative events such as the occurrence of hypotension, bradycardia, and patient movement were noted. All patients were given ondansetron 0.1 mg/kg and paracetamol 1 gm IV towards the end of surgery. Propofol infusion was stopped after completion of skin suturing; nitrous oxide was turned off after arm-sling was applied. The LMA was removed once the patient was fully awake and obeyed commands. Time to spontaneous eye opening, obeying simple verbal commands and removal of PLMA (recovery time) after stopping propofol infusion were recorded. The total amount of propofol and fentanyl used were noted. On emergence from anesthesia, patients were asked to rate the severity of pain according to VAS. Postoperatively, all patients were shifted to neuro-intensive care unit for further management where they received IV paracetamol 1 gm, eight hourly. HR, MAP, SpO2, respiratory rate (RR), and VAS were recorded at periodic intervals up to 24 h after the surgery. Fentanyl 0.5 μg/kg was administered when VAS (0–10) was ≥4 and repeated every 10 min till the VAS was less than 4. VAS scores, fentanyl usage and any complications during the postoperative period were recorded for 24 h of surgery.

Statistical analysis

Statistical analysis was performed with Stata 15.1 for Windows (StataCorp, College Station, Texas). The Student's t test was used for inter-group comparison of mean values of various parameters (demographic data, intraoperative input–output, durations of surgery and anesthesia, propofol and fentanyl consumption, recovery time, postoperative analgesia consumption, etc.). A P < 0.05 was considered significant. Values of hemodynamic parameters, BIS, temperature, and VAS were analyzed by using generalized estimating equations to detect intra- and inter-group differences at various time points.

 Results



A total of 62 patients met the eligibility criteria for inclusion in the study; two patients refused to participate [Figure 1]. Hence, a total of 60 patients were included with 30 in each arm (Groups B and S). The demographic characteristics of patients in both groups were comparable [Table 1]. All the patients were classified as ASA physical status I except one patient in Group S, who had hypertension. The mean duration of pain before surgery was also comparable in both groups. SGB was successful in the first attempt in 56 patients (28 in each group). In two patients of each group, two attempts were required. In Group B patients, signs of successful SGB were apparent within 10 min of the procedure on the side of the block, but clinical manifestations were variable: ptosis (100%), conjunctival congestion (90%), miosis (80%), vasodilation of the upper limb (90%), and enophthalmos (86.67%). Eighteen patients (60%) reported of complete relief of pain of the affected limb after SGB. While performing the SGB, accidental vessel puncture occurred in four patients (two in each group). No patient developed any other complication or the features of motor block. Intraoperative parameters such as HR, MAP, BIS, and temperature were comparable in the two groups at baseline and at various stages of surgery [Table 2]. HR, MAP, skin temperature, and VAS scores were compared before and after the administration of SGB [Table 3]. No significant change was found in HR before and after the block in either group. However, MAP was found to be significantly lower in patients of Group B after the block (P = 0.02). The skin temperature of the affected limb increased significantly after SGB in patients of Group B (P < 0.001), whereas no change was found in other group. VAS score after the block was significantly lower in both the groups, but the magnitude of change was greater in Group B.{Figure 1}{Table 1}{Table 2}{Table 3}

Intraoperative anesthetic consumption, as indicated by the requirement of propofol and fentanyl, was significantly less in Group B than in Group S [Table 4]. The average propofol consumption in Group B was 1659.7 ± 787.5 mg compared with 2500.7 ± 740.9 mg in Group S (P = 0.0003). The intraoperative fentanyl consumption in Group B was 190 ± 82.5 μg vs. 327.3 ± 139.3 μg in Group S (P = 0.0001). As a consequence, recovery time (time taken from stopping propofol to the time of PLMA removal) was also significantly shorter in patients of Group B.{Table 4}

In the postoperative period, except for few episodes of nausea and shivering no other complications were noted during the first 24 h. It was found that the requirement of postoperative analgesics was markedly lower in Group B and the time to first analgesic was also significantly longer in this group [Table 5]. The postoperative HR, MAP, and VAS score recorded at various time intervals during the first 24 h were comparable between the two groups. This may attest to timely administration of analgesics in the patients of both groups.{Table 5}

 Discussion



The concept of preemptive analgesia was introduced to prevent the deleterious effects of noxious stimuli, consequent allodynia, and increased pain. It is possible that antinociceptive treatment is more effective in reducing postoperative pain if started before surgery than when started later.[17] The contribution of the sympathetic nervous system to the pathogenesis of chronic pain is extensively described in the literature. In the setting of chronic pain, the role of SGB is established as it interrupts pain cycle, reduces sympathetic tone, prevents central sensitization, and helps to restore normal somatic sensation. In contrast, the potential for the sympathetic nervous system to contribute to acute nociceptive pain has not been widely studied. It was traditionally believed that acute nociceptive pain is detected and transmitted solely through the somatic nervous system and that perioperative multi-modal analgesia targets only the somatic nervous system at various levels. Our study attempts to add one more dimension to this concept by providing support for the hypothesis that the sympathetic nervous system is also involved in the pathogenesis of acute pain. One plausible explanation is that the sympathetic nervous system, which is normally inactive, becomes activate following injury or surgery.[3],[18] The reduction in pain might be due to alteration in the concentration of endogenous neurotransmitters, improvement in blood flow and washing out of inflammatory mediators in the blocked arm, thus modulating and attenuating the activity of A-delta and C-fibers.[10],[11],[19],[20],[21],[22] We targeted the stellate ganglion as a means of isolating the contribution of the sympathetic system to acute nociceptive pain.

In this study, a significant decrease was found in the intraoperative consumption of propofol and fentanyl in Group B. This is probably due to sustained pain relief provided by the local anesthetic. Typically, these surgeries require large doses of opioids and high concentrations of anesthetic agents to prevent patient movement, as muscle relaxants are avoided to facilitate neuromuscular monitoring. However, such high doses of opioids and anesthetics may cause nausea, vomiting, sedation, delayed recovery, and respiratory depression. Many of these patients are on chronic pain medications; hence, it is also prudent to provide opioid-sparing or opioid-protective anesthetic techniques to avoid iatrogenic increase in the intensity of postoperative pain.[23] In this study, postoperative analgesia requirement and VAS scores were also significantly lower in Group B. Postoperative pain in patients undergoing surgical repair of BPI have both neuropathic and inflammatory components.[11] It is possible that SGB relieved the neuropathic (sympathetic) component of pain, and systemic analgesic drugs relieved the inflammatory component.

Kakazu and Julka [12] have studied the involvement of the sympathetic nervous system in acute pain following fracture of humerus. They found reduction in VAS scores from 10 to 0 within 5 min of SGB. McDonnell et al.[11] observed an excellent postoperative analgesia and decreased requirement of opioids for 48 h after SGB with lidocaine. Kumar et al.[14] in a randomized controlled study compared the analgesic efficacy of preoperative SGB on postoperative pain relief after upper limb orthopedic surgery and showed a postoperative reduction in oral opioid requirement, in the study group. Some studies suggest that the duration of analgesia after SGB can last up to 72 h in patients with chronic pain.[24],[25] However, we only wanted to examine the role of sympathetic block in treating early postoperative pain, thus, we did not continue observations beyond 24 h. Further studies will be required to establish such long-term benefits.

Placebo response has been shown to have a tremendous impact on pain outcomes following sympathetic blocks in patients with chronic neuropathic pain, yet it has often been neglected or unrecognized.[26],[27],[28],[29],[30] On the basis of available evidence, we cannot refute that placebo effect can contribute substantially to pain relief obtained after SGB. Hence, we included a placebo group (Group S) in our study and found significant lowering of VAS score even after SGB using normal saline, but the magnitude of fall was much greater in the bupivacaine group [Table 3]. McGuirk et al.[31] questioned the use of invasive placebos, in randomized controlled trials, because of the potential for harmful effects. They described a “SHAM” (Serious Harm and Morbidity) scale to assess the risk [0: no risk (no intervention), 1: minimal risk (noninvasive placebo action), 2: minor risk (minimally invasive placebo), 3: moderate risk (invasive placebo intervention), 4: major risk (invasive placebo procedure)].[31],[32] This study would be classified as SHAM grade 4. A sham puncture followed by injection of 10-mL saline was used to ensure maximum internal validity, blinding, and unbiased assessment. The safety of the patients was ensured throughout the placement of the block as experienced anesthesiologists performed the block with strict asepsis. None of the patients had any serious procedure-related complications. Serious complications such as subarachnoid or vertebral artery puncture may occur following SGB at a frequency of 1.7 in 1000 blockades.[33] Volumes >5 mL can spread to distant structures such as the carotid baroreceptor and vagus nerve leading to occurrence of Horner's syndrome and hoarseness of voice.[34],[35] The blind technique also carries some risk of injury to the vertebral artery and rarely, pneumothorax.[36] Kastler et al. reported that SGB with 10-mL bupivacaine 0.25% at C6–C7 using fluoroscopy resulted in transient side-effects in 84% of patients.[37] Another study using computed tomography-guided SGB at the C7 and T1 vertebral levels found no complications in the blockade group.[38]

The development of Horner's syndrome has been used to indicate success when performing SGB. In our study, we observed all the patients for 10 min postinjection for the development of features of sympatholysis. All our patients developed ipsilateral ptosis, but other features such as miosis, enophthalmos, conjunctival congestion, and vasodilation of upper limb were not uniformly present. However, some studies have suggested that clinical signs such as Horner's syndrome are not an essential indicators for correct placement of the local anesthetic during SGB.[25],[34],[39] Another study proposes a combination of increase in skin temperature and negative sweat test in the blocked arm as confirmatory evidence of successful SGB.[40] However, all these variables are yet to be validated.

To the best of our knowledge, no published study has evaluated the potential benefits of SGB on intraoperative anesthetic and analgesic consumption. However, this study does have certain limitations. Firstly, the anatomy of the stellate ganglion is variable and even though the blocks were performed by experienced anesthesiologists, there are problems inherent to all “blind” procedures. It is possible that the entire volume of test drug was not uniformly deposited in the desired anatomic location in all patients. Existing literature suggests that ultrasound-guided SGBs may provide better quality pain relief than blind blocks in CPRS.[41] Perfect blinding of the anesthesiologist might not have been possible at all times because the clinical manifestations of SGB could not be concealed. Further limitations of the study are that patients were not stratified according to the stage of CPRS and long-term outcomes were not studied. It was beyond the scope of this study to study the effect of adjuvants when used along with local anesthetics for the block. Finally, as it is a small study, larger trials will be required to corroborate the findings of our study and establish potential intraoperative and postoperative benefits of SGB in other groups of patients undergoing surgery.

 Conclusion



In this study, a decrease was observed in intraoperative anesthetic and analgesic requirement with SGB using bupivacaine in patients with CPRS II undergoing surgical repair. Similarly, in the postoperative period, there was also decreased requirement of opioids and an increased duration to when the first analgesic was required. However, this is a small study and larger studies are required to validate these findings.[42]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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