TY - JOUR
AU - P, Vercauteren, Marcel
AB - Abstract Objective To use quantitative sensory testing (QST) to assess whether a stellate ganglion block (SGB) modulates the analgesia induced by cervical paravertebral block (CPVB). Design A prospective double-blind randomized controlled trial. Setting Department of Anesthesia, Antwerp University Hospital, October 2011 to December 2015. Subjects Twenty-eight adults scheduled for arthroscopy of a nonfractured shoulder were enrolled. Methods Participants were randomly assigned to receive either single CPVB (5 mL of levobupivacaine 0.5%) or combined CPVB + SGB (5 mL and 3 mL of levobubivacaine 0.5%, respectively). The detection thresholds for cold/warm sensations and cold/heat pain were established using thermal QST on the C4-C7 dermatomes before local anesthetic infiltration and at 0.5, 6, 10, and 24 hours thereafter. Our primary outcome was the time course of QST thresholds for the different neurosensitive/nociceptive modalities. As secondary and tertiary outcomes, we evaluated the degree of motor block and the time to first administration of rescue analgesics. Results We randomized 20 patients. There were no significant differences in the detection thresholds for the neurosensitive/nociceptive modalities, motor block, or timing for rescue analgesics between the groups (P = 0.15–0.94). All patients with CPVB + SGB exhibited Horner’s signs, whereas patients in the CPVB group did not exhibit these signs; however, this does not exclude sympathetic block. Conclusions We were unable to demonstrate any analgesic benefit of CPVB + SGB in arthroscopic shoulder surgery. It is therefore not unreasonable to suppose that pain from soft tissue injuries without bony lesions is transmitted mainly by somatic nerves with no or only minimal involvement of the sympathetic nervous system.  Neurosensory Effects, Combined Cervical Paravertebral-Stellate Ganglion Block, Somatic-Sympathetic Interaction Introduction Participation of the sympathetic nervous system in pain generation has been best described in chronic and typically neuropathic pain states, such as complex regional pain syndrome; however, its contribution to the generation/processing of acute somatic pain requires elucidation. In contrast to animal data, surprisingly little is known about the modulation of nociceptive information by the sympathetic nervous system in humans [1]. Chronic neck and shoulder pain can induce sympathetic activation in a patient scheduled for elective surgery. For example, sensory fibers of an arthritic shoulder joint may respond to sympathetic activity [2]. Furthermore, surgical insult or trauma can be the priming needed before the sympathetic nervous system can relay perioperative pain [3,4]. Sympathetic ganglia, especially the stellate ganglion, have been the target of blockade by local anesthetics (LAs) for the diagnosis and treatment of sympathetically mediated pain. A sympathectomy is proposed to interrupt the pain cycle, facilitate rehabilitation of the painful area, and help restore balanced somatic sensation [5]. However, the role of a stellate ganglion block (SGB) in the treatment or prevention of acute pain following upper limb surgery or trauma remains controversial. McDonnell et al. [4] performed SGB before the surgical repair of severe upper limb trauma and achieved considerable reduction of postoperative opioid requirements. Kumar et al. [6] demonstrated the efficacy of preoperative SGB for pain relief after surgical repair of upper limb fracture. In contrast, Choi et al. [5] were unable to find any benefit of SGB on the visual analog scale (VAS), vital signs, and analgesic requirements during the 48 hours after arthroscopic shoulder surgery. To clarify inconsistencies in the available evidence, further studies should focus on the role of the sympathetic nervous system in the generation of acute postoperative pain [2]. We therefore evaluated the efficacy of SGB to modulate the analgesic effects induced by cervical paravertebral block (C5-CPVB or C5-root block) in a double-blind randomized controlled trial (RCT). The novelty of this study was the use of quantitative sensory testing (QST) to monitor the magnitude and time course of the regional block. QST was used because it allows the effect of LAs on A-δ and C-fibers to be assessed quantitatively [7–9]. For this purpose, the detection thresholds for various neurosensitive/nociceptive modalities as measured by QST were compared in carefully selected young adults who were randomly assigned to receive regional anesthesia (RA) with either a single CPVB or combined CPVB + SGB, while undergoing arthroscopic surgery on a non–chronically diseased and nonfractured shoulder. Methodology In this single-center, prospective, double-blind RCT, patients scheduled to undergo a shoulder arthroscopy were considered to receive either single CPVB or combined CPVB + SGB. Patients with possible abnormal QST findings (i.e., those receiving opioids or chronic analgesic therapy for more than three weeks or suffering from peripheral neuropathy caused by diabetes or other etiologies) or with contraindications for RA, such as coagulation problems, were excluded. The patients in both patient groups suffered from shoulder disease with similar pathology. The indications for the shoulder arthroscopy were acute and subacute lesions (Table 1). By assessing QST preoperatively, we could exclude chronic pathology and central sensitization. Table 1 Demographic data and quantifiable patient characteristics Patient Characteristics Group 1: CPVB Group 2: CPVB + SGB Quantitative data  N 10 10  M/F ratio 6/4 6/4  Age, y 51 (34–55) [31–68] 54 (47–57) [26–64]  Height, cm 172 (166–176) [164–178] 173 (154–178) [152–183]  Weight, kg 78.0 (71.0–84.0) [63.5–98.0] 79.0 (65.0–84.7) [47.0–102.0]  BMI, kg/m2 27.0 (23.4–29.7) [22.8–31.6] 25.8 (22.0–27.5) [21.6–33.7]  Duration of operation, min 31.5 (14.4) [22.6–40.5] 27.3 (12.9) [19.3–35.3] Shoulder pathology  Instability of shoulder with recurrent dislocation 1 1  Shoulder pain due to impingement syndrome 2 1  Post-traumatic shoulder impingement – 1  Degenerative rotator cuff disease 6 7  Calcific tendinitis 1 – Rescue medication  Paracetamol 1 g + Ketorolac 30 mg i.v. 9 6  Paracetamol 1 g i.v. 2 6  Tramadol 100 mg i.v. 1 3  Paracetamol 1 g per os 2 4  No analgesics 1 3 Patient Characteristics Group 1: CPVB Group 2: CPVB + SGB Quantitative data  N 10 10  M/F ratio 6/4 6/4  Age, y 51 (34–55) [31–68] 54 (47–57) [26–64]  Height, cm 172 (166–176) [164–178] 173 (154–178) [152–183]  Weight, kg 78.0 (71.0–84.0) [63.5–98.0] 79.0 (65.0–84.7) [47.0–102.0]  BMI, kg/m2 27.0 (23.4–29.7) [22.8–31.6] 25.8 (22.0–27.5) [21.6–33.7]  Duration of operation, min 31.5 (14.4) [22.6–40.5] 27.3 (12.9) [19.3–35.3] Shoulder pathology  Instability of shoulder with recurrent dislocation 1 1  Shoulder pain due to impingement syndrome 2 1  Post-traumatic shoulder impingement – 1  Degenerative rotator cuff disease 6 7  Calcific tendinitis 1 – Rescue medication  Paracetamol 1 g + Ketorolac 30 mg i.v. 9 6  Paracetamol 1 g i.v. 2 6  Tramadol 100 mg i.v. 1 3  Paracetamol 1 g per os 2 4  No analgesics 1 3 In most cases, the surgery consisted of rotator cuff debridement with an arthroscopic shaver. In both groups, there was one procedure with minimal arthroscopic rotator cuff repair (labeled as “Instability of shoulder with recurrent dislocation”). Values indicate the mean (SD) [95% confidence interval], median (interquartile range) [range], or number. Rescue medication: number of patients. Table 1 Demographic data and quantifiable patient characteristics Patient Characteristics Group 1: CPVB Group 2: CPVB + SGB Quantitative data  N 10 10  M/F ratio 6/4 6/4  Age, y 51 (34–55) [31–68] 54 (47–57) [26–64]  Height, cm 172 (166–176) [164–178] 173 (154–178) [152–183]  Weight, kg 78.0 (71.0–84.0) [63.5–98.0] 79.0 (65.0–84.7) [47.0–102.0]  BMI, kg/m2 27.0 (23.4–29.7) [22.8–31.6] 25.8 (22.0–27.5) [21.6–33.7]  Duration of operation, min 31.5 (14.4) [22.6–40.5] 27.3 (12.9) [19.3–35.3] Shoulder pathology  Instability of shoulder with recurrent dislocation 1 1  Shoulder pain due to impingement syndrome 2 1  Post-traumatic shoulder impingement – 1  Degenerative rotator cuff disease 6 7  Calcific tendinitis 1 – Rescue medication  Paracetamol 1 g + Ketorolac 30 mg i.v. 9 6  Paracetamol 1 g i.v. 2 6  Tramadol 100 mg i.v. 1 3  Paracetamol 1 g per os 2 4  No analgesics 1 3 Patient Characteristics Group 1: CPVB Group 2: CPVB + SGB Quantitative data  N 10 10  M/F ratio 6/4 6/4  Age, y 51 (34–55) [31–68] 54 (47–57) [26–64]  Height, cm 172 (166–176) [164–178] 173 (154–178) [152–183]  Weight, kg 78.0 (71.0–84.0) [63.5–98.0] 79.0 (65.0–84.7) [47.0–102.0]  BMI, kg/m2 27.0 (23.4–29.7) [22.8–31.6] 25.8 (22.0–27.5) [21.6–33.7]  Duration of operation, min 31.5 (14.4) [22.6–40.5] 27.3 (12.9) [19.3–35.3] Shoulder pathology  Instability of shoulder with recurrent dislocation 1 1  Shoulder pain due to impingement syndrome 2 1  Post-traumatic shoulder impingement – 1  Degenerative rotator cuff disease 6 7  Calcific tendinitis 1 – Rescue medication  Paracetamol 1 g + Ketorolac 30 mg i.v. 9 6  Paracetamol 1 g i.v. 2 6  Tramadol 100 mg i.v. 1 3  Paracetamol 1 g per os 2 4  No analgesics 1 3 In most cases, the surgery consisted of rotator cuff debridement with an arthroscopic shaver. In both groups, there was one procedure with minimal arthroscopic rotator cuff repair (labeled as “Instability of shoulder with recurrent dislocation”). Values indicate the mean (SD) [95% confidence interval], median (interquartile range) [range], or number. Rescue medication: number of patients. Patients enrolled were given premedication with lorazepam 1 mg per os and discontinued preoperative analgesics, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and/or paracetamol, 12 hours before surgery. The study was performed at the Antwerp University Hospital from October 2011 to December 2015. After approval by the Institutional Ethical Committee (11/20/162), the research project was conducted in accordance with the recommendations of good clinical practice. Written informed consent was obtained from all participants. Sealed envelopes containing random allocation cards with computer-generated random numbers were used to randomly allocate participants to receive either a single CPVB or a combined CPVB + SGB (Figure 1). These envelopes were prepared by an independent researcher who was not involved in the study. The sealed envelope was given to an unblinded anesthetist who performed the block. Figure 1 View largeDownload slide Consort 2010 flow diagram. Figure 1 View largeDownload slide Consort 2010 flow diagram. The CPVB approach was ultrasound-guided and targeted at the level of the emerging fifth cervical nerve root. Under sterile conditions, a linear 18-MHz ultrasound (US) transducer (Focus 800, BK Ultrasound, Herlev, Denmark) and a 22-gauge needle (Sonoplex 50 mm, Pajunk, Geisingen, Germany) were used. The C5 root was localized by recognizing the transverse processes of C7, C6, and C5. The needle was positioned lateral to and below the C5 root, and 5 mL of 0.5% levobupivacaine (LBup 0.5%; Chirocaine, Abbvie SA, Wavre, Belgium) was slowly injected. To minimize subdural injection in the root-specific block, which has the potential to damage axons and/or influence our results, we combined the following techniques: 1) to minimize subdural positioning of the needle, we used a peripheral nerve stimulator with low current intensity, avoiding motor response by direct stimulation of axons [10,11], and 2) we performed a peri-plexus injection and tangential approach of the roots [12–16]. The injection site of the SGB was localized using the linear US transducer, and a lateral approach was performed. The transducer was placed transverse to the anterior scalene muscle, with the carotid artery medial and the brachial plexus lateral and a few millimeters caudal to the prominent anterior tubercle of C6 (Chassaignac’s tubercle). The needle was inserted in plane lateral and posterior to the carotid artery and directed to the longus colli muscle [17]. The needle tip was positioned in the plane formed by the prevertebral fascia and the longus colli muscle. Slowly, 3 mL of 0.5% LBup was injected. All patients who received the combined block exhibited Horner’s signs, whereas none of the patients in the single CPVB group had evidence of these signs. We did not measure the differences in temperature between the ipsi- and contralateral side as this method is ineffective if the skin is warm at the onset of the block [18]. Moreover, the QST device will start delivering a change in temperature (either heating up or cooling down) only when the skin temperature underneath the surface of the thermode is within a normative range (determined by the hardware; normative range of skin temperature as measured by the thermode: 31.4°C–32.6°C). We were unable to hide the Horner’s signs from the nurse performing the QST and the anesthetist in charge of the general anesthesia. As all QST responses rely on the patients’ perception, neither the nurse assisting the QST measurement nor the anesthetist in charge of the anesthesia was able to interfere with the threshold assessment. General anesthesia was induced after the second QST assessment with 3 μg/kg of fentanyl, 2–3 mg/kg of Propofol, and 0.5 mg/kg of rocuronium and maintained using sevoflurane. Noninvasive blood pressure (NIBP), electrocardiography (ECG), SpO2, and capnography were monitored either continuously (ECG, SpO2, and capnography) or at regular intervals (NIBP). Increments of opioid were administered when the pre-induction blood pressure increased by >25%. Thermal QST (TSA-II – NeuroSensory Analyser, Medoc Ltd, Ramat Yishai, Israel) was performed within dermatomes C4 through C7. The thermal analyzer thermode was placed on the dermatomes to be tested; it induces a serial change in temperature starting at a baseline of 32°C. The surface temperature of the thermode changed at a rate of 1°C/s for non-noxious sensations and 1.5°C/s for painful stimulations. Patients set threshold values by pressing a button when they detected a change in temperature or pain. The detection thresholds for non-noxious cold and warm sensations (representing the A-δ fibers and C-fibers, respectively) were recorded first. The detection thresholds for cold and heat pain (both representing the A-δ and C-fibers) were subsequently documented. To avoid skin injury, increases and decreases in temperature were stopped at 50.5°C for heat pain and 0°C for cold pain. The QST analyzer software (Win TSA 5.32, Medoc Ltd, Ramat Yishai, Israel) uses the gender, age, and dermatome to identify corresponding normative values for the different thermal thresholds [19]. Thermal QST was performed at one hour before US-guided CPVB (baseline control value) and at 0.5, 6, and 10 hours; and at 21 to 24 hours after LA infiltration. QST was established in fully cooperative patients either before (baseline and at 0.5 hours following LA injection) or after full recovery from general anesthesia (at 6, 10, and 21 to 24 hours after LA injection). The third (first postoperative) QST was performed at six hours postinjection of the LA, thereby avoiding any residual anesthesia effects. Patients with baseline QST control values that indicated the presence of hyper- or hyposensory phenomena were excluded. In each dermatome (C4, C5, C6, and C7) and at each of the assessment times, five serial measurements were obtained for cold/warm sensation (CS/WS), and three serial measurements were obtained for cold/heat pain (CP/HP). The average of the serially measured detection thresholds was considered. To obtain a within-subject control value, the detection thresholds were also tested in the contralateral (unblocked) C5 dermatome. WS/CS and HP/CP detection thresholds were established by applying the reaction-time-inclusive method of limits. Individual baseline values were used as substitute reference ranges for the normative data available for these tests. The effect of applying RA was assessed by evaluating the differences in detection thresholds for these non-noxious thermal stimuli. The degree of hypoesthesia was expressed as an absolute value of the temperature change of the detection threshold between the baseline (32°C) and maximal level (50.5°C for WS and 0°C for CS) [19]. Following each QST, the degree of motor block was evaluated using a validated three-point modified Bromage scale [20]. A score of 2 indicated no motor block, a score of 1 indicated decreased motor strength, and a score of 0 indicated complete motor block with an inability to move. Patient demographics, quantifiable characteristics, preoperative medication, shoulder pathology, and surgery duration were also noted. In addition, both the need for and timing of rescue analgesic medication were noted in the medical records. The rescue medication consisted of 1 g of paracetamol and 30 mg of ketorolac administered intravenously (i.v.). Assuming a 50% difference in magnitude and duration of regional block between a single CPVB and a combined CPVB + SGB approach and supposing equal variability in both groups (expected standard deviation of 37.5% in both groups), 10 patients were required in each group (α = 0.05 and β = 0.8) [21]. Our primary outcome was the time course of QST thresholds for the different neurosensitive/nociceptive modalities at dermatomes C4–C7. As a secondary outcome, we evaluated the degree of motor block. As a third outcome, we considered the time to rescue analgesics. Repeated measures analysis of variance (ANOVA) was performed to compare the mean differences in outcomes for QST over different time points (baseline and after 0.5, 6, 10, and 24 hours post-treatment) or dermatomes (C4, C5, C6, and C7) between groups that were defined by the blocks to which they were assigned. Additionally, outcome data were modeled using the generalized estimating equation (GEE) approach. The advantage of GEE consists of greater flexibility when handling different types of outcomes (e.g., continuous QST and noncontinuous motor block tests) and the ability to model a wide variety of correlation patterns between the repeated measures [22]. The times to the first request for rescue analgesic and the VAS scores at these occasions were compared between the single CPVB and the combined CPVB + SGB groups using survival analysis with parametric and nonparametric tests. Our null hypothesis assumed no significant difference between the single CPVB and the combined CPVB + SGB groups for the times to rescue analgesic requirement and the VAS scores at these moments. A value of P < 0.05 was considered significant. Data analysis was performed using Stata (version 14, StatCorp, College Drive, TX, USA). Results Twenty-eight eligible patients were included in the study. The subjects were randomly assigned to two study groups to undergo either CPVB or CPVB + SGB. After an interim evaluation, we ultimately analyzed the results of 20 patients, with a sample size of 10 patients in each group (Figure 1). Patient demographics and quantifiable characteristics were similar across the two groups (Table 1). The QST results prior to injection were within the age-, sex-, and dermatome-specific normative ranges for all 20 patients [19]. With reference to within-dermatome differences in detection thresholds for the different neurosensitive (WS and CS) and nociceptive (HP and CP) modalities, the following observations could be made. In both the CPVB and CPVB + SGB treatment groups, the detection thresholds for WS, CS, HP, and CP at dermatome C5 and for WS and CP at dermatome C6 after 0.5, 6, and 10 hours following treatment were found to be significantly different (P < 0.01–0.001) from the corresponding values before and at 21 to 24 hours following LA injection. At the C4 level, the thresholds for WS at six hours (CPVB and CPVB + SGB) and at 10 hours (CPVB) and those for HP at 10 hours (CPVB and CPVB + SGB) were found to be significantly higher. At the C6 level, the thresholds for CS at six hours (CPVB and CPVB + SGB) and for CP at 0.5 and six hours (CPVB) were significantly higher after peri-plexus administration of 0.5% LBup. In the C7 dermatome, the thresholds for neurosensitive modalities did not change significantly for any of the times assessed (P = 0.844). In the C4–C7 dermatomes, the baseline (pretreatment) threshold values for the investigated neurosensitive modalities were not significantly different from those measured at 24 hours following LA injection. Regarding between-dermatome differences in detection thresholds for the neurosensitive (WS and CS) and nociceptive (HP and CP) modalities, the following conclusions could be made. At 0.5, 6, and 10 hours following LA injection, thresholds for WS, CS, HP, and CP at the C5 level were significantly different from the corresponding values measured at the other levels (C4, C6, and C7). The thresholds for WS, CS, HP, and CP for both CPVB and CPVB + SGB at C4, C5, C6, and C7 are represented in Tables 2–5 (Supplementary Data). The time course of WS and CS thresholds for CPVB and CPVB + SGB for C5 and C6 are shown in Figures 2 and 3, respectively. The between-dermatome differences for WS and CS at 0.5 hours following LA injection are shown in Figure 4. Figure 2 View largeDownload slide Magnitude and time course of the detection thresholds for warmth and cold sensation, after single cervical paravertebral block (CPVB; ◆) or combined CPVB +  stellate ganglion block (●) at the ipsilateral (◆ and ●, respectively) and contralateral (open symbols) C5 dermatomes. Symbols indicate mean, with error bars representing the 95% confidence intervals. Figure 2 View largeDownload slide Magnitude and time course of the detection thresholds for warmth and cold sensation, after single cervical paravertebral block (CPVB; ◆) or combined CPVB +  stellate ganglion block (●) at the ipsilateral (◆ and ●, respectively) and contralateral (open symbols) C5 dermatomes. Symbols indicate mean, with error bars representing the 95% confidence intervals. Figure 3 View largeDownload slide Magnitude and time course of the detection thresholds for warmth and cold sensation, after single cervical paravertebral block (CPVB; ◆) or combined CPVB + stellate ganglion block (●) at the ipsilateral C6 dermatome. Symbols indicate the mean, with error bars representing the 95% confidence intervals. Figure 3 View largeDownload slide Magnitude and time course of the detection thresholds for warmth and cold sensation, after single cervical paravertebral block (CPVB; ◆) or combined CPVB + stellate ganglion block (●) at the ipsilateral C6 dermatome. Symbols indicate the mean, with error bars representing the 95% confidence intervals. Figure 4 View largeDownload slide Between-ipsilateral dermatome differences in the magnitude of detection thresholds for warmth and cold sensation, after cervical paravertebral block (CPVB) using low-volume, high-concentration, and long-acting local anesthetic, targeted at the C5 level. This CPVB block was administered alone (◆) or combined with ipsilateral stellate ganglion block (●). Symbols indicate the mean, with error bars representing the 95% confidence intervals. Figure 4 View largeDownload slide Between-ipsilateral dermatome differences in the magnitude of detection thresholds for warmth and cold sensation, after cervical paravertebral block (CPVB) using low-volume, high-concentration, and long-acting local anesthetic, targeted at the C5 level. This CPVB block was administered alone (◆) or combined with ipsilateral stellate ganglion block (●). Symbols indicate the mean, with error bars representing the 95% confidence intervals. At 30 minutes, motor block was complete (Grade 2) in 9/10 patients in the CPVB group and in 5/10 patients in the CPVB + SGB group. A decreased (Grade 1) motor response was observed in 1/10 and 5/10 participants in the CPVB and CPVB + SGB groups, respectively. However, it cannot be excluded that impaired mobility of the shoulder due to the pathology or the surgical procedure may have interfered with the rating of the motor block. Finally, differences in the corresponding values among the treatment groups for neurosensitive modalities (WS, CS, HP, and CP) and motor block according to the three-point modified Bromage scale were not sufficient to exclude the possibility that the differences were simply due to sampling variability (P = 0.15–0.94) (Tables 2–5 and Figures 2–5). Figure 5 View largeDownload slide Time course of motor block after single cervical paravertebral block (CPVB; ◆) or combined CPVB + stellate ganglion block (●) at the ipsilateral site, as evaluated using the three-point modified Bromage scale. Symbols indicate the mean, with error bars representing the 95% confidence intervals. Figure 5 View largeDownload slide Time course of motor block after single cervical paravertebral block (CPVB; ◆) or combined CPVB + stellate ganglion block (●) at the ipsilateral site, as evaluated using the three-point modified Bromage scale. Symbols indicate the mean, with error bars representing the 95% confidence intervals. The times to the first request for rescue analgesic were 9.3 hours (interquartile range [IQR] = 9.1–9.4 hours, range = 9.0–10.0 hours) and 9.3 hours (IQR = 9.0–9.4 hours, range = 8.7–9.8 hours), and the VAS scores for these time intervals were 6.0 (IQR = 5.0–6.0, range = 4.0–7.0) and 6.2 (IQR = 5.3–7.8, range = 4.0–10) for the single CPVB and combined CPVB + SGB groups, respectively. Neither the times to first request for rescue analgesic (P = 0.51) nor the VAS scores at these occasions were significantly different (i.e., P = 0.51 and 0.33 for the timing and the VAS scores, respectively). The log-rank test for equality of survivor functions (Χ2 = 1.46, with 1 degree of freedom, P = 0.227) did not demonstrate any significant difference in the time to analgesic requirement between the CPVB and the combined CPVB + SGB groups (Figure 6). Therefore, the null hypothesis assuming no differences between the timing and VAS scores of single CPVB and combined CPVB + SGB cannot be rejected. Figure 6 View largeDownload slide Survival analysis referring to the patient’s survival without rescue medication. Solid and dotted lines represent single cervical paravertebral block (CPVB) and combined CPVB + stellate ganglion block, respectively. Figure 6 View largeDownload slide Survival analysis referring to the patient’s survival without rescue medication. Solid and dotted lines represent single cervical paravertebral block (CPVB) and combined CPVB + stellate ganglion block, respectively. Discussion Although the role of the autonomic nervous system in the pathogenesis of chronic pain is clearly defined, its potential to facilitate acute nociceptive transmission has been scarcely documented. To investigate any such presumed sympathetic nervous system involvement in the modulation of acute somatic pain, we evaluated whether SGB could contribute to the antinociceptive effect of RA by C5-CPVB for elective surgery on a nonfractured shoulder. The assumed benefits of this combined approach (by adding SGB to CPVB) refer to an earlier onset, prolonged duration, increased magnitude, and greater extent of the nerve block, which is measured using QST. As the sensory fibers responsible for the transmission of nociception and temperature sensation (the A-δ and C-fibers) are similarly affected by LBup 0.5%, changes in the temperature sensation indicate that the regional block is working in the indicated area [23,24]. We, therefore, considered all of the neurosensitive/nociceptive modalities when detecting the possible contribution of SGB to a CPVB. The novelty of this study was that we used QST to monitor the magnitude and time course of the regional block. A CPVB, which was first performed by Pippa et al. [25] with a posterior approach to avoid the vertebral artery and vein, is performed at the root level, before the anterior and middle scalene fibers cross over. At that level, as they exit the neuroforamina to reach the cervical paravertebral space, the roots are divided into anterior motor nerves and posterior sensory nerves [25–27]. The injection of small volumes of LA solution posterior to the nerve root can explain why the C5-CPVB (root block) causes less motor block than the traditional ISB (trunk block) [28]. Such an ISB is performed distally to the point where the C5 and C6 roots have penetrated the cross-over point of the anterior and middle scalene muscles and join together to form (mixed sensory and motor) the brachial plexus’s upper trunk. With these small volumes of LBup 0.5% administered in the single CPVB group, we might expect no cervical ganglia blockage [29–31]. From the detection thresholds for the tested neurosensitive/nociceptive modalities in both the single CPVB and the combined CPVB + SGB treatment groups, we could confirm a stable sensitive and nociceptive block at the C5 level with maximal effect between 0.5 and 10 hours following the injection of LA. Furthermore, with the low-volume, high-anesthetic concentration used, the block at the C5 level started earlier and was more profound than the block obtained in the neighboring (C4 and C6) dermatomes. These observations suggest a reduced/delayed effect due to the ongoing spread of the LA solution from the C5 level. With this approach and this volume of LA, C7 nerve roots may not be blocked. Finally, we were unable to demonstrate any added analgesic benefit of combining SGB to CPVB for treating acute pain caused by arthroscopic surgery on a non–chronically diseased and nonfractured shoulder joint. We exclusively enrolled subjects scheduled to undergo surgery on soft tissues and specifically disqualified those with bony pathology and fractures from the trial (Table 1). The short duration of the surgery (Table 1) and the relatively high postoperative VAS scores indicate that the majority of participants underwent extensive rotator cuff debridement and very few repairs (Table 1). Although arthroscopic techniques are commonly claimed to reduce postoperative pain, these benefits typically are seen only after the first few days following the procedure [32]. Rotator cuff surgery is associated with very sharp and localized soft tissue pain that is relayed to the central nervous system (CNS) through somatic nerves. Therefore, if we assume that the two groups were clearly defined in that one group had a pure somatic nerve block (CPVB) and the other a pure somatic nerve block combined with a perfect sympathetic block (CPVB + SGB), then it is not unreasonable to expect that the analgesia obtained in both groups should be similar. Following long bone fractures, patients experience immediate acute, stabbing, and excruciating (“worst imaginable”) pain that is referred to the site of injury. If the fractured bone is splinted and movement is reduced within minutes to hours following the initial trauma, the pain decreases to a dull and aching discomfort that may be moderate on resting and may be exacerbated by different movements or positions [33]. The quality of patient pain descriptions vary, blurring the boundaries between deep somatic or visceral pain. Deep somatic pain from many deep somatic elements, for example, bones and joints, shares many features with visceral pain, including poor somatotropic localization, referral of pain to distant sites, and a particular ability to generally increase CNS excitability, which manifests as elevated motor and autonomic reflexes. Additionally, unmyelinated (C) or thinly myelinated (A-δ) fibers from many deep somatic elements mainly reach the central nervous system through autonomic pathways, thereby traversing the sympathetic chain [34–37]. Because efferent sympathetic (and parasympathetic) fibers and visceral afferents travel within the same nerves, the consequences of treatment procedures inevitably affect both afferent and efferent nerves. However, it is likely that pain relief after sympathetic nerve interruption is more satisfactorily explained by the effect of the procedure on sensory (including visceral) afferents that course with the efferent sympathetic fibers [38]. These fellow-traveling afferents lead to visceral-type/deep somatic pain [39]. Previous studies have shown that efferent autonomous nerve fibers may play a significant role in driving skeletal pain [40,41]. Under physiological conditions, sympathetic outflow is well known to have no effect on nociceptor function and activity [3,42]. Trauma, that is, fracture [2,6,43], seems to be the priming needed before efferent sympathetic nerve fibers can modulate sensory nerve fiber function (sympathetically maintained pain) [44]. Based on previous observations, the following hypothesis can be proposed. First, nociceptive stimulation of soft tissues is a well-perceived and -localized event that is encoded and conveyed primarily by the somatic nerves. Second, orthopedic surgery (i.e., fracture repair) and conditions affecting bones result in a visceral type of pain that is relayed to the CNS via afferent sympathetic nerves. This framework allows us to reconcile the apparently conflicting evidence in the literature. Choi showed that there is no advantage to sympathetic block in patients undergoing arthroscopic shoulder surgery, while McDonnel and Kumar showed significant postoperative pain relief and analgesic sparing effects after SGB [4,6]. Their patients underwent orthopedic surgery for fracture repair of the upper limb. Interestingly, the “confusion” in the literature is not really confusing. In cases of bone pain, SGB helps manage the pain, and if only soft tissue surgery is performed, it does not. This seems to be a consistent theme in the properly performed studies reported in the literature, and in this respect the current trial is no exception. The use of SGB solely for the management of acute nociceptive pain has scarcely been documented. A recent meta-analysis found only a single study with level-1B evidence and a handful of series with level-1 C evidence on the use of SGB [45]. Although many authors have stated the effectiveness of SGB, there is a paucity of high-quality evidence. We share the views of Chambers and Smith [46], who discussed the series by McDonnell et al. and cautioned against using SGB for postoperative analgesia in routine practice, as the mechanism is not completely understood. QST refers to a group of procedures for assessing the perceptual responses to quantifiable stimuli to characterize somatosensory function. QST establishes the integrity of the entire neural axis from the level of the receptors to the brain. As such, QST can provide information regarding the thinly myelinated A-δ- and small unmyelinated C-fiber function. This test is an important addition to the neurophysiologic armamentarium because conventional sensory nerve conduction reflects only large fiber function and is less sensitive for detecting the activity of the smaller myelinated and unmyelinated fibers that mediate pain sensation. Pinprick stimulation, accomplished by gently stimulating the skin with a needle, activates predominantly A-δ-fibers [47]. Moreover, the method used in the current study to clinically evaluate the efficacy of the regional block is the motor block, which evaluates the functional integrity of descending motor pathways. QST can evaluate various aspects of pain processing and might therefore be able to monitor and predict the analgesic efficacy of a given drug [7]. Sermeus et al. [8] demonstrated the utility of QST for detecting the occurrence/characteristics of sensory block induced by RA. Furthermore, changes in detection thresholds for various neurosensitive/nociceptive modalities, as measured by QST, have been demonstrated to correlate with the analgesic response to SGB [9]. The results of QST are highly dependent on the methodology and the full cooperation of the subject. QST has been shown to be reasonably reproducible over a period of days or weeks in normal subjects [48]. Some potential risks and limitations of the current study must be considered. The first is the small number of patients who were included. The current study used QST to compare the ability of two RA techniques to relieve the pain associated with arthroscopic surgery of the shoulder. We selected our population carefully using rigid inclusion criteria, as described in the text, to reduce between-patient variability. However, this approach inevitably introduced constraints, such as the availability of large numbers of patients within a reasonable period of time. Because of this new approach to regional block testing, no historical data were available from related studies. Assuming a clinically meaningful difference of 50% [49] and a standard deviation of 75% of this value (i.e., 37.5%), 10 patients would be required in each group [21]. The present trial had various purposes, such as testing study procedures, assessing the recruitment rate, and estimating parameters such as the variance of the outcome variable to calculate the sample size. The current study may provide pilot data to explore the utility of QST in the acute pain setting. Second, there is a concern that a CPVB may result in sympathectomy given that sympathetic fibers travel along the brachial plexus and, even with a small local anesthetic volume, excluding the possibility of blocking the sympathetic fibers would be very difficult as they may join the plexus nerves as early as the roots. The stellate ganglion receives neural input from the paravertebral sympathetic chain and sends sympathetic efferents to the cervical trunks of the brachial plexus. The spread of the LA from the cervical paravertebral space to the sympathetic chain, inducing objective evidence exhibited by Horner’s syndrome, appears to be more frequently associated with larger LA injection volumes [28,50–53]. To the best of our knowledge, no reports of Horner’s syndrome can be found after using 5 mL of local anesthetic solution to perform CPVB. In the current investigation, none of the patients receiving single CPVB had Horner’s signs, whereas all of the patients receiving CPVB + SGB exhibited Horner’s signs. However, by performing a paravertebral (root) block, sympathetic outflow may be blocked at the level of the grey rami communicantes, which run from C5 and C6 to the middle cervical ganglion. Although grey ramus communicantes provide the greatest source of innervation to the vertebral column, most preganglionic sympathetic efferents innervating the head, neck, and upper extremity either pass through or synapse at the stellate ganglion [54]. Occasionally, additional sympathetic innervation to the upper extremity exits the sympathetic chain via grey rami communicantes at T2 and T3 and goes on to the distal upper extremity without ever passing through the stellate ganglion. These anomalous pathways have been termed Kuntz’ nerves. Given the high reported success rates of SGB in providing a total sympathetic block of the arm [2,55], the contribution of the grey rami communicantes, including the Kuntz’ nerves to the sympathetic innervation of the arm, appears to be limited [56]. Moreover, many clinical pain syndromes of the upper limb have been treated using a single SGB [1,4,6]. Third, the lack of pain relief despite a clinically apparent effective sympathetic blockade can occur. Obviously, if the pain is truly independent of activity in the sympathetic nervous system, no pain relief is expected. The more difficult problem is ascertaining whether or not sympathetic blockade in the area of interest has actually occurred [57]. Determination of the adequacy or completeness of the sympathetic block is difficult and contentious, and there is no defined method to confirm a full block. An absolute increase in index finger or hand temperature and asymmetry in the hand temperature after SGB often fails to predict pain relief [9,58]. Other tests, such as the resistance response, sweat test, or laser skin blood test, require elaborate equipment and specific expertise [58–60]. Fourth, although QST provides quantifiable sensory measures, similar to other psychophysical methods, it can be affected by variations in the subject’s concentration, attention, and disposition and by procedural variability. Moreover, as with clinical pain, individual differences in QST responses have been associated with multiple biopsychosocial mechanisms that have also been found to influence clinical pain [48]. Although the reliability of heat and cold pain detection thresholds appeared to be lower, sufficient consistency and reproducibility for thermal QST changes have been confirmed in different studies [48,59]. The majority of the sensory assessment methods in RA, that is, pinprick stimulation, rely on skin tests because the tegumental sensory apparatus is readily accessible [47]. We are not aware of any method that tests the small fibers at the level of the periosteum or bone. Fifth, the lack of a placebo group makes changes in subjective thermal QST measurements difficult to attribute to either a regional block or a natural resolution. RCTs in pain management techniques often prove to be underpowered, which can be attributed to the difficulty of motivating patients and referring physicians to participate in a trial where there is considerable probability of receiving a placebo/sham/nonsedating medication for severe postoperative pain. QST assessment requires that the subject is alert, cooperative, and able to follow instructions. Opioid analgesics or ketamine could, therefore, interfere with QST assessments because of their concomitant sedative effects. Furthermore, the validity of a sham intervention as a reflection of the natural course of the disease is questioned. Any new technique should prove to be at least equally as effective as the best available treatment option, which offers the possibility of comparing two groups that both receive active treatment [61]. Sixth, the model proposed does not preclude the possibility that epinephrine from the adrenal medulla contributes to the sensitization of nociceptors after injury. This effect may be caused by the humoral component of the sympathetic response, which is not controlled by the nerve block. The use of QST in RA offers some challenges and future opportunities. First, in future trials, patient selection should be less restrictive, that is, trauma patients should also be enrolled. Furthermore, the inclusion of a patient group receiving a single SGB would allow the determination of the unbiased effects of sympathetic block on various thermal neurosensitive/nociceptive QST modalities in the clinical setting. Second, logistical issues, such as the space and expense of the QST equipment as well as the time required to complete the assessments, may be a barrier to implementation in clinical settings. Future technological development should aim to make the QST faster, less cumbersome, and more user friendly [9]. Third, investigations that applied multimodal testing procedures frequently found that LAs differ in their ability to inhibit stimuli of different natures [9]. The sensitivity, specificity, and predictive values of sensory tests in relation to the surgical stimuli have not been investigated. Research in this field would provide useful information for daily clinical practice. In conclusion, we were unable to demonstrate any added antinociceptive benefit of the addition of a stellate ganglion block to a cervical paravertebral block for treating acute pain caused by arthroscopic surgery on a non–chronically diseased and nonfractured shoulder joint. It is therefore not unreasonable to suppose that pain from soft tissue injuries without bony lesions is transmitted mainly by somatic nerves with no or only minimal involvement of the sympathetic nervous system. There is a growing body of evidence confirming that “bone pain” resembles a visceral type of pain, which is relayed via sympathetic nerves, while soft tissue injury incites nociceptive pain that is conveyed by somatic nerves. These premises would allow us to reconcile the apparently conflicting evidence in the literature. If there is evidence of “bone pain,” SGB helps manage the pain, and if there is only soft tissue injury without any bony lesions, SGB does not help. Acknowledgments The authors wish to thank Kristien Wouters for checking the statistical analysis. Supplementary Data Supplementary Data may be found online at http://painmedicine.oxfordjournals.org. 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TI - Effects of Stellate Ganglion Block on Analgesia Produced by Cervical Paravertebral Block as Established by Quantitative Sensory Testing: A Randomized Controlled Trial
JF - Pain Medicine
DO - 10.1093/pm/pny004
DA - 2018-11-01
UR - https://www.deepdyve.com/lp/oxford-university-press/effects-of-stellate-ganglion-block-on-analgesia-produced-by-cervical-iVUPWowB6N
SP - 2223
VL - 19
IS - 11
DP - DeepDyve
ER -