I read with interest the report of Hanling et al^[1] in the May issue of the ASRA News “Stellate Ganglion Block for Posttraumatic Stress Disorder: A Call for Clinical Caution and Continued Research.” The authors suggested in the report that stellate ganglion block (SGB) lacks efficacy for the treatment of posttraumatic stress disorder (PTSD). Essentially, the ASRA News article was a summary of a 2016 publication in Regional Anesthesia and Pain Medicine, where the first randomized, blinded, sham-controlled study was performed at the Naval Medical Center San Diego.^[2] The purpose of the current communication is to clarify certain comments as to SGB use for PTSD treatment.

From a historical perspective, we were the first to report the use of SGB for treating PTSD in 2008.3 The following should be noted:

1. SGB should be performed on the right side to address PTSD: “This is likely because initial case series happened to be performed on the right side in the patients with pain conditions.”^[1] Actually, our 2010 article discussed SGB as being performed by using right-sided preference and that this was necessary because of the known right-sided amygdala activation noted in PTSD^[4] as well as subsequent descriptions by Alkire et al^[5] in 2015. Furthermore, SGB was used to treat PTSD because of a rational prediction of the effect, based on the work of Telaranta^[6] with endoscopic thoracic sympathectomy used to treat anxiety and PTSD. The history of the evolution of SGB as a viable treatment for PTSD was documented in a 2012 publication by our team in the peer-reviewed Journal of Affective Disorder. ^[7]
2. “Correlation with current functional MRI (fMRI) studies has not provided a convincing model to date.”^[1] That is true; however, no fMRI studies have been conducted to assess this issue. Yet, neuroimaging studies have been done and were published by Alkire et al^[5] in 2015. They used two separate fluorodeoxyglucose positron-emission tomography (PET) brain scans, the first prior to SGB and the second post SGB. PET is considered by some as being more specific than fMRI for the diagnosis of PTSD. The patients in the PET study were drawn from the VA Long Beach Healthcare System in Long Beach, California. The authors' conclusions were as follows: “SGB had efficacy for significantly reducing PTSD symptoms in a rapid and sustained manner.”^[5] The right amygdala and hippocampal areas appear to be relatively overactive when PTSD symptoms are prominent and become deactivated following SGB.^[5] Alkire et al^[5] used the Clinically Administered PTSD Scale (CAPS) as the diagnostic and follow-up tool for PTSD (as did Hanling et al^[1] in their study). On follow-up, Alkire et al^[5] were able to demonstrate CAPS reduction that mirrored right-sided amygdala deactivation. The 2016 report by Hanling et alx has recently been evaluated by a Veterans Administration evidencebased synthesis program.^[8] The determinations of this synthesis are summarized below.

The study essentially compared ultrasound-guided SGB with 5 mL of 0.5% ropivacaine to an inactive sham SGB procedure performed with normal saline solution in 42 male military participants with both combat and noncombat PTSD. SGB was administered on the right side of the neck, generally at the C6 level.^[8] Although in previous case series the most commonly used anesthetic type and dosage have been 7 mL of ropivacaine or a bupivacaine 0.5% solution, this trial used 0.5% ropivacaine, a 28% lower dose, and provided no rationale for doing so. Although the stellate ganglion is typically located anatomically between C6 and C7, the level of target needle placement was C5 to C6 in this study.^[8]

Although the study authors confirmed that the injection was typically at C6, some could have been at C5 and may have missed the stellate ganglion.^[8] The use of saline instead of an active control that mimicked the side effects of SGB was potentially inadequate and may have reduced the effectiveness of the blinding, as patients may have been able to easily tell if they received local anesthetic SGB or the sham block, based on the occurrence of the Horner's syndrome–expected ptosis. Effectiveness of the blinding was not formally assessed.^[8] Finally, there were more active-duty participants in the SGB group (96% vs 73%), attrition was high overall (57%)—primarily because they were “lost to follow-up at 3 month post treatment or completed outside of 3 month posttreatment window”—and was higher in the SGB group (67% vs 40%), and the study did not report on or account for potential between-group differences in concurrent PTSD treatments.^[8] “Because these findings come from a single study with imprecise findings, moderate methodological limitations, and did not directly focus on clinically relevant outcomes or use the most commonly administration techniques and anesthetics, they provide an insufficient basis upon which to draw conclusions about SGB for the treatment of PTSD in Veterans.”^[8] At the conclusion of the ASRA News article by Hanling et al,^[1] a question was raised as to why the results are so different between the retrospective study by Mulvaney et al^[9] in which 166 patients had marked improvement and the study conducted at the Naval Medical Center San Diego that did not do better than placebo. One large difference is the population group that Hanling et al^[2],[8] studied. The patients undergoing SGBs may have been inappropriate for the study because most were in the process of undergoing a disability evaluation and may have had secondary financial incentives to resist treatment.^[2],[8] Marked improvement in PTSD symptoms has been shown at five independent medical institutions: Mulvaney et al^[9] at Walter Reed Medical Center; Alino et al^[10] at Tripler Army Hospital; Alkire et al^[5] at Long Beach, California, Veterans Administration; Hicky et al^[11] at the Naval Medical Center San Diego; and Lipov et al^[3-4] at the Advanced Pain Centers. To date, more than 2,500 military personnel have been treated with SGB with good to very good success (unpublished).

Hanling et al^[1] went on to discuss potential rare but “catastrophic risk” of SGB as one of the reasons SGB should not be used to treat PTSD. Wulf and Maier^[12] conducted a single, large study of SGB risks in 1992 (pre ultrasound or fluoroscopic-guidance era) in which 45,000 SGBs were performed. The incidence of severe complications was 1.7 in 1,000 blockades. No fatalities were reported. Most complications were related to the central nervous system toxicity from rapid local anesthetic absorption (ie, convulsions).^[12] A high subarachnoid block was reported in six cases, high epidural blockade in three, pneumothorax in nine, and allergic reactions in two patients.^[12] It is likely that in the current ultrasound and/or fluoroscopic guidance era, where imaging is widely accepted as being a standard of care, further reductions will occur in reported complications. Given the known suicide risk associated with PTSD of 22 per day,^[13] a possible complication rate of 1.7 out of 1,000 pales by comparison (0.17%). Furthermore, PTSD symptoms are positively correlated with suicide risk.^[14] Finally, SGB has been reported to impact suicidal ideation.^[10],[15]

In summary, I believe that the randomized controlled trial by Hanling et al^[2] should not prevent practitioners from offering SGB as a valued and safe treatment for PTSD. A well-powered study is being conducted in three sites at Womack Army Medical Center, with disability evaluation patients excluded for reasons associated with secondary gain issues. One of the limitations of the current study is the lack of fMRI response monitoring. Veterans Administration evidence-based synthesis program recommends an fMRI evaluation in a study where SGB is used to treat PTSD symptoms.^[8]

References

1. Hanling S, Fowler I, Hackworth R. Stellate ganglion block for posttraumatic stress disorder: a call for clinical caution and continued research. ASRA News. May 2017;10–14.
2. Hanling SR, Hickey A, Lesnik I, et al. Stellate ganglion block for the treatment of posttraumatic stress disorder: a randomized, double-blind, controlled trial. Reg Anesth Pain Med 2016;41(4):494–500. doi: 10.1097/AAP.0000000000000402.
3. Lipov EG, Joshi JR, Lipov, Sanders SE, Siroko MK. Cervical sympathetic blockade in a patient with post-traumatic stress disorder: a case report. Ann Clin Psychiatry 2008;20(4):227–228. doi: 10.1080/10401230802435518.
4. Lipov E. Successful use of stellate ganglion block and pulsed radiofrequency in the treatment of posttraumatic stress disorder: a case report. Pain Res Treat 2010;2010:963948. doi: 10.1155/2010/963948.
5. Alkire MT, Hollifield M, Khoshsar R, Nguyen L, Alley S, Reis, C. Neuroimaging suggests that stellate ganglion block improves post-traumatic stress disorder (PTSD) through an amygdala mediated mechanism. Paper presented at: Anesthesiology 2015 Annual Meeting; October 24, 2015; San Diego, CA. Available at: http://www.asaabstracts.com/strands/asaabstracts/abstract.htm;js essionid=0CAC170518A556F620F2245A983B8314?year=2015&index=5&absn um=3003. Accessed September 3, 2017.
6. Telaranta T. Treatment of social phobia by endoscopic thoracic sympathectomy. Eur J Surg 1998;164(S1):27–32.
7. Lipov E, Kelzenberg B. Sympathetic system modulation to treat post-traumatic stress disorder (PTSD): a review of clinical evidence and neurobiology. J Affect Disord 2012;142(1–3):1–5. doi: 10.1016/j.jad.2012.04.011.
8. Center C, Peterson K, Bourne D, Anderson J, Mackey K, Helfan, M. Evidence Brief: Effectiveness of Stellate Ganglion Block for Treatment of Posttraumatic Stress Disorder (PTSD). Washington, DC: Department of Veterans Affairs; 2017.
9. Mulvaney SW, Lynch JH, et al. Stellate ganglion block used to treat symptoms associated with combat-related post-traumatic stress disorder: a case series of 166 patients. Mil Med 2014;179(10):1133–1140. doi: 10.7205/ MILMED-D-14-00151.
10. Alino J, Kosatka D, McLean B, Hirsch K. Efficacy of stellate ganglion block in the treatment of anxiety symptoms from combat-related post-traumatic stress disorder: a case series. Mil Med 2013;178(4):e473–e476. doi: 10.7205/ MILMED-D-12-00386.
11. Hicky A, Hanling, S, Pevney E, Allen R, McLay RN. Stellate ganglion block for PTSD. Am J Psychiatry 2012;169(7):760. doi: 10.1176/appi.ajp.2012.1111172.
12. Wulf H, Maier C. Complications and side effects of stellate ganglion blockade: results of a questionnaire survey. Anaesthesist 1992;41(3):146–151.
13. Kemp J, Bossarte R. Suicide Data Report: 2012. Washington, DC: Department of Veterans Affairs, Mental Health Services, Suicide Prevention Program; 2013.
14. McKinney JM, Hirsch JK, Britton PC. PTSD symptoms and suicide risk in veterans: serial indirect effects via depression and anger. J Affect Disord 2017;214:100–107. doi: 10.1016/j.jad.2017.03.008.
15. Lipov E. Marked impact on suicidal ideation and suicidology in a military populations following a cervical sympathetic blockade. In: Guide to the 2015 Annual Meeting: Integrating Body and Mind, Heart and Soul; May 14, 2015; Toronto, Canada. Abstract 802.