Learning Objectives/Outcomes: After participating in this CME/CNE activity, the provider should be better able to:
1. Review the history and diagnostic criteria of posttraumatic stress disorder (PTSD).
2. Describe currently available treatment options.
3. Explain the mechanism of action and interpret the evidence on use of stellate ganglion blocks to treat PTSD.
4. Identify potential complications involved with use of stellate ganglion block in treatment of PTSD.
Posttraumatic stress disorder (PTSD) is a severe mental health disorder that can develop after experiencing or witnessing a traumatic event such as combat, natural disaster, or sexual assault. It is characterized by a reexperiencing of the traumatic event via upsetting memories, nightmares, flashbacks, or emotional distress.1 The American Psychiatric Association has provided several criteria for the diagnosis of PTSD in the DSM-5.1Table 1 lists a summary of some of the factors required for diagnosis.
Patients begin to avoid situations that trigger these feelings, which leads to social isolation and disturbances in relationships. PTSD was first described by the American Psychiatric Association in the 1980s when it was incorporated as a diagnosis in the Diagnostic and Statistical Manual of Mental Disorders-3rd edition (DSM-III) and has since shown increasing incidence, given improved awareness and better detection.
Additionally, ongoing large-scale military conflicts in Afghanistan and Iraq continue to place many members of the military and private contractors in higher-risk environments that can lead to development of this disorder. It is the third-highest prevalent diagnosis made (11.96%) in veterans returning from conflicts in Iraq and Afghanistan, behind pain (48.5%) and depression (12.56%).2 The prevalence of PTSD in the United States is reported to be 6.8% in the general population.3
Current treatment options available for PTSD include a combination of pharmacologic therapies and psychotherapies. The pharmacologic therapies include selective serotonin reuptake inhibitors, serotonin norepinephrine (NE) reuptake inhibitors, anticonvulsants, and antipsychotics. The psychotherapies include cognitive behavioral therapy, cognitive processing therapy, prolonged exposure, eye-movement desensitization, and reprocessing.4
There are also a number of complementary and alternative therapies available, such as mindfulness, yoga, and acupuncture, that have been shown to be helpful, albeit on a small scale.5 Overall, however, successful treatment of PTSD remains a challenge, with over one-third of patients failing to recover after many years of treatment.6
In addition to the high rish of treatment failure, patients face many barriers to treatment, and a stigma associated with treatment options. Surveys conducted on veterans returning from Operation Enduring Freedom or Operation Iraqi Freedom who screened positive for PTSD indicate that 40% of these veterans had concerns about treatment consequences. They were most often concerned about the need for prescription psychotropic medications and about even a potential impact on their employment. Other barriers identified include emotional readiness for treatment, stigma, and logistical issues involved with seeking care, such as transportation management.7
Veterans Administration health services provide veterans with excellent access to psychotherapies. In the general population, however, access to similar therapies remains challenging, given financial constraints and lack of insurance coverage for many available therapies.8
Given the limitations and hesitations for patients suffering from PTSD to undergo current evidence-based treatment, innovative approaches that could potentially offer a biological approach may be more accessible, and may provide the faster results that are needed.
History of Stellate Ganglion Block
Use of stellate ganglion block (SGB) was first reported in the literature in the 1940s and 1950s. During those decades' time, cervical sympathectomy and SGB were being researched as beneficial procedures for treatment of neuropsychiatric disorders such as epilepsy, migraine headache, and cerebral hemorrhage.9 It was during this period that Karnosh et al10 published a case series noting mood alterations as a consequence of SGBs including euphoria, especially in patients with known depression.
A subsequent article by the same research team reviewed their experience with more than 500 patients who underwent ganglionectomy after successful SGBs reporting increased feeling of "self-security" and reduced anxiety.11 Similarly, research during the 1950s began to demonstrate not only improved mood and reduced symptoms of depression, but also improvement in patients affected by early dementia and psychosis.12
Anatomy Related to SGB
The stellate ganglion is a collection of nerve cell bodies of the sympathetic nervous system located between the C6 and C7 vertebrae. In about 80% of people, the ganglion is formed by a fusion of the inferior cervical ganglion and the first thoracic ganglion. A small percentage of the populations (between 10% and 20%) have T2 contributions to the stellate ganglion called Kuntz nerve fibers. It typically measures 2.5 x 1 x 0.5 cm and lies between the vertebral artery and the longus colli muscle and is medial to the common carotid artery and the jugular vein.13
Preganglionic fibers from the anterolateral column of the spinal cord merge in the area located between the subclavian artery and in front of the first rib. From the ganglion, postganglionic fibers travel down to provide virtually all sympathetic innervation to the head, neck (through the sympathetic chain), and upper extremities [through cervical nerves (C7-C8) and first thoracic nerve (T1)]. Injection of local anesthetic around the ganglion inhibits transmission of the sympathetic outflow to the head, neck, and upper extremity.
Technique and Imaging Guidance for Administering SGB
There are several ways to perform SGB using anatomic landmarks, fluoroscopic guidance, and ultrasound guidance. Currently, the gold standard is the ultrasound-guided technique. For this technique, the patient is placed supine with the neck extended and the head rotated slightly to the contralateral side of the block.14 An ultrasound transducer is placed at the level of cricoid cartilage perpendicular to the trachea scanning caudally to find the C6 vertebral body and Chassaignac's tubercle. The thyroid gland, carotid artery, internal jugular, thyroid gland, C6 spinal nerve, longus colli, and longus capitis muscles are also identified.
At this point, local anesthetic is administered at the skin via a small skin wheal. Following this, a 22-G or 25-G, 3.5-inch spinal needle is guided in plane until the tip is located at the prevertebral fascia within the fascia of the longus colli muscle, between the carotid artery and C6 anterior tubercle. At this point, local anesthetic can be injected with intermittent gentle aspiration while observing for local spread of local anesthetic.15
Although no single local anesthetic is used, the general recommendation is 5 to 20 mL of local anesthetic for successful stellate ganglion blockade.16 This acts to block the sympathetic nervous system impulses to the head, neck, and upper extremities. Successful placement of the block is confirmed by presence of Horner's syndrome, clinically noted by the presence of ptosis, anhydrosis, and miosis on the ipsilateral side. An increase in temperature to the ipsilateral upper extremity is also noted (Figure 1).
Proposed Mechanisms
Although the exact mechanism of SGB in PTSD treatment is not known, there have been many hypothesized mechanisms for the actions of SGB on PTSD pathway. SGB is shown to cause profound vasodilation and sympathetic blockade of the cervical nerve roots, which may contribute to the overall mechanism.
The most popular theories discuss the effects of local anesthetic in decreasing nerve growth factor (NGF), which is shown to be increased in periods of acute and chronic stress, and brain levels of NE.
A study by Westerhaus and Lowery17 demonstrated increased activity of the amygdala associated with patients with PTSD. Increased levels of NGF have been shown to increase perivascular NE levels, further contributing to the PTSD cascade.
This stress-induced release of NE has been linked to anxiety-like behavioral responses as well.18 A study by Jeong et al19 demonstrated that administration of bupivacaine during SGB in rats significantly reduced electroencephalogram activity, causing a sedative effect. Other studies done on human subjects demonstrated similar sedative effects when lidocaine was used for SGB.20 Elevation in NE levels is what is targeted by the proposed SGB to potentially alleviate symptoms of PTSD and reverse the PTSD cascade.
The theory is that by "resetting" the sympathetic nervous system with local anesthetic, this allows for the system to function physiologically. However, any potential benefit from the block may fade in some patients, when the local anesthetic effect wears off.
Some practitioners add corticosteroid with the hope of prolonging the effect, and some have even attempted pulsed radiofrequency (PRF) ablation of the ganglion. Recent case reports and a few small-scale animal studies have shown the clinical benefit of radiofrequency ablation of the stellate ganglion in limb ischemia, PTSD, and Reynaud's syndrome.21-23
A 2010 case report by Lipov21 showed a major reduction in anxiety after an SGB. However, symptoms returned after 1 month. After this, a PRF ablation was performed with a 22G 10-cm insulated needle with a 10-mm active tip. The patient reported immediate relief and relief lasted about 4 months after that.21
These studies are promising and suggest that patients who benefit from SGB could demonstrate longer-lasting success in symptom management with ablation therapy. However, at this time, no large-scale studies have been done to evaluate PRF ablation for patients who have benefitted from SGB that is short-lived. PRF is a technique where a short, high-voltage current is applied in bursts, and which is related to thermal continuous radiofrequency. However, PRF does not cause tissue destruction and coagulative necrosis as does standard thermal continuous radiofrequency ablation. The mechanism by which PRF provides analgesia is unclear but may involve a neuromodulatory effect in synaptic signaling.24
Literature is currently lacking on the use of surgical stellate ganglionectomies for PTSD. In the cardiology literature, rats that underwent a bilateral surgical stellate ganglionectomy seemed to have reduced cardiac remodeling and fibrosis theorized to be a result of less sympathetic neurohormonal expression and reduced activity of the renin angiotensin system.25
Evidence for Use of SGB in PTSD
Since the realization of the benefits of SGB on different psychiatric conditions, many articles have been published demonstrating the benefits of SGB in the treatment of PTSD. Lipov et al26 authored a study of the first reported case of improvement of PTSD with SGB. The case described a 48-year-old male victim of armed robbery who initially underwent psychotherapy, focusing on relaxation techniques, but still experienced debilitating anxiety. He underwent a right-sided C6 SGB with 7 mL of 0.5% bupivacaine and reported immediate improvement in his symptoms. He endorsed improvement of his symptoms of anxiety and reduced hypervigilance for 32 days after receiving SGB. When his symptoms returned, he underwent a PRF ablation of the right stellate ganglion, which allowed him 90% improvement at a 3-month follow-up visit.26
Since then, many case studies and series have shown improvements in patients with PTSD with SGB. An initial publication by Mulvaney et al27 showed 2 cases where right-sided SGB at C6 level resulted in immediate relief of PTSD symptoms. A few years later Mulvaney et al28 published the largest case series to date that looked at 166 active duty service members over a 6-month period. All 166 patients received a right-sided C6 SGB, with more than 70% showing clinically significant improvement in a PTSD symptom checklist.
Following such positive results in many case series, a randomized, double-blind, controlled trial was conducted by Hanling et al.29 A total of 42 male military participants with both combat and noncombat PTSD underwent either a right-sided SGB at C6 with 5 mL of 0.5% ropivacaine or sham procedure with saline.
Participants were assessed at 1 week, 1 month, and 3 months after the procedure, and patients in the sham group were allowed to cross over into the treatment group whereas participants who still experienced symptoms after 1 SGB were allowed to receive a second block.
Overall, there were no statistically significant differences in PTSD symptoms between the treatment and sham groups. However, some criticisms of the study include:
* The lower volume of local anesthetic used in the study-5 mL versus the usually reported 7 mL;
* The fact that some SGB was being performed at the C5 level versus C6; and
* Potential secondary gain in participants regarding disability benefits.29
Further research is currently being conducted, including a multisite randomized controlled trial with a goal of 240 participants who are active duty service members, to determine whether a statistically significant difference can be revealed.30
Potential Complications
Complications to SGB, although rare, can be very serious, given the proximity of other important structures. A 2016 Cochrane Review on SGB for complex regional pain syndrome listed adverse events, finding that 0% to 14% of SGBs performed in the studies reviewed experienced an adverse event. Complications reported include dizziness, blurred vision, puncture pain, increased pain, headache, nausea, vomiting, dysphagia/hoarseness (related to inadvertent blockade of the recurrent laryngeal nerve), hematoma, dyspnea, shivering, cold feeling, face swelling, and mouth numbness.31
Rare complications such as "locked-in" syndrome have also been reported, along with other serious complications related to intra-arterial injection of local anesthetic leading to central nervous system or cardiac toxicity.32 Given the proximity to the spinal column, it is possible to inject local anesthetic into the epidural or intrathecal space, which may produce a total spinal anesthesia requiring airway management.
A 1992 study by Wulf and Maier33 reported 1.7 complications per 1000 blocks, although recent use of ultrasound guidance has even further reduced the rate of complications when compared with previous blind or fluoroscopic techniques.
Conclusion
PTSD is a common psychiatric condition affecting millions of veterans and other Americans that often goes untreated. Currently available treatment options provide inadequate relief of symptoms for many patients and come with major barriers and stigma. SGB has developed into a potential treatment mechanism to provide long-term relief for these patients. SGB as potential treatment for PTSD has shown quite remarkable evidence of support. Immediate and long-term effects of SGB have led to promising prospects of treatment for these patients, with demonstrated improvements in mood, sleep quality, and anxiety.
A few of the many advantages of SGB include its high rate of efficacy and reduction in polypharmacy, which may lead to profound improvement to the quality of life for the millions of people suffering from this disorder. Although promising results were seen in case series, results from a randomized controlled trial were inconclusive. Further research is ongoing, and perhaps with inclusion of the general population to increase the number of participants, statistically significant improvements may be uncovered.
References