Long Acting Liposomal Bupivacaine for Percutaneous Sympathetic Stellate Ganglion Blockade: A Technical Note

Abstract

Introduction

We describe the use of long acting liposomal bupivacaine for percutaneous stellate ganglion blockade to treat severe headaches following internal carotid artery dissection.

Methods

A 43-year old woman developed right-sided refractory headache after right internal carotid artery dissection. Patient underwent percutaneous stellate ganglion block using bupivacaine hydrochloride (0.25%–20 ml) in the past with short acting relief. Liposomal bupivacaine (EXPAREL) 13.3 mg/mL (1.3%) solution diluted with preservative-free normal saline: a total solution of 20 ml (52 mg of bupivacaine) was injected at the level of the lower portion of body of the sixth cervical vertebra, medial to the right internal carotid artery. The response to sympathetic block was assessed by a neurologist not involved in the procedure.

Results

After the stellate ganglion block with bupivacaine hydrochloride, patient was headache free immediately after the block but with recurrence of pain on Day 3 with return to peak intensity by Day 4. After the stellate ganglion blockade with liposomal bupivacaine hydrochloride, patient reported recurrence of pain on Day 15 post injection with return to peak intensity by Day 17. The patient reported an episode of aura which consisted of visual scintillations on Day 2 which lasted for five days and resolved spontaneously.

Conclusion

Liposomal bupivacaine injection for stellate ganglion blockade can result in a more prolonged effect compared with bupivacaine hydrochloride.

INTRODUCTION

Percutaneous sympathetic blockade using local injection of anesthetic agent within the paravertebral muscle compartment, which contains the cervical sympathetic fibers and stellate ganglion, has been used for multiple indications. Such indications include treatment of sympathetic dysnergia involving upper extremity such as Raynaud’s phenomenon [1], cardiac ventricular tachycardia storm [2, 3], and more recently, refractory pain related to internal carotid artery dissection [4]. Bupivacaine hydrochloride (Marcaine) is commonly used and is available in sterile isotonic solutions at 0.25% and 0.5% concentrations for injection via local infiltration. The onset of action is within 2–10 min, and the effect may last up to 7 h after alveolar injection for dental procedures. However, a longer duration of sympathetic blockade is desirable due to persistent dysnergia in several disease processes. Liposomal bupivacaine (Exparel, Pacira Pharmaceuticals, San Diego, CA, USA) is a long-acting formulation of bupivacaine loaded in multi-vesicular liposomes. Local infiltration can result in significant bupivacaine systemic plasma concentrations for up to 96 h [5, 6]. The use of liposomal bupivacaine for cervical sympathetic block has not been reported previously. We report the results in a woman with refractory pain secondary to internal carotid artery dissection who demonstrated temporary relief following bupivacaine hydrochloride injection.

CASE DESCRIPTION

A 43-year-old female physician developed right-sided headache after right internal carotid artery dissection, involving the high cervical and petrous segments confirmed by cerebral angiography. The headache was initially accompanied by Horner’s syndrome, which resolved over the next few months. On evaluation six months after internal carotid artery dissection, the persistent daily headache was described as sharp with self-reported severity varying between 3–6/10 on numeric pain scale, which interfered with sleep and ability to work. There was variable and limited response to medications including intravenous lidocaine and dihydro-ergotamine infusion.

Patient underwent percutaneous sympathetic stellate ganglion blockade using bupivacaine hydrochloride (0.25%–20 ml) at eight-month post dissection. An independent neurologist not involved in the procedure assessed the response to sympathetic block. Patient remained headache free immediately after the stellate ganglion block for three days with return to peak intensity by Day 4. However, she was able to resume professional duties in the ensuing weeks. Due to exacerbation of headaches, a second stellate ganglion blockade using bupivacaine hydrochloride (0.25%–20 ml) was performed at 12-month post dissection. After the second stellate ganglion block, patient remained headache free immediately after the blockade again for three days with return to peak intensity by Day 4. Patient reported erythema over the site of injection and right distal upper extremity numbness without any clear dermatomal pattern. The numbness resolved in four days after injection. Patient developed transient ptosis and miosis after each injection. No further stellate ganglion blockades were pursued due to temporary nature of the pain relief.

Due to persistent and debilitating nature of the headaches, liposomal bupivacaine was considered to ensure a more sustained sympathetic blockade. The use of liposomal bupivacaine for stellate ganglion block was reviewed and approved by the Institutional Pharmacy Committee. A right stellate ganglion blockade was performed using a low (test) dose of liposomal bupivacaine at 16-month post dissection. A second stellate ganglion blockade was performed using standard dose equivalent of liposomal bupivacaine 11 days after the test dose blockade. A third stellate ganglion blockade was performed using higher dose of liposomal bupivacaine 18 days after the second blockade.

TECHNIQUE

The procedure was performed under conscious sedation. A total of 3 ml of 1% lidocaine was infiltrated to anesthetize the skin and superficial subcutaneous tissues. A 22-gauge × 3.5-inch BD Quincke spinal needle was introduced at the level of the lower portion of body of the sixth cervical vertebra, medial to the right internal carotid artery. The needle was advanced until it reached the junction between the body and the transverse process of the sixth cervical vertebra [Figure 1(A) and (B)]. The position of the needle was confirmed by contrast injection, which demonstrated the needle anterior to the paravertebral muscles, with spread along the axis of the interfascial compartment (see Figure 2). Liposomal bupivacaine was injected over 10 min in each procedure with monitoring of blood pressure and heart rate.

Figure 1(A) and (B). AP and lateral projections demonstrating the tip of needle at junction between the body and transverse process of the sixth cervical vertebra.

Figure 2. The position of the needle was confirmed by contrast injection, which demonstrated the needle anterior to the para-vertebral muscles, with spread along the axis of the interfascial compartment.

PREPARATION AND INJECTION OF LIPOSOMAL BUPIVACAINE

Liposomal bupivacaine EXPAREL (bupivacaine liposome injectable suspension) is available as a 13.3-mg/mL (1.3%) solution in a 20-mL single-use vial. Liposomal bupivacaine was administered after dilution with preservative-free normal (0.9%) saline. EXPAREL vial was inverted multiple times to re-suspend particles immediately prior to withdrawal from the vial, and diluted suspensions were used immediately after preparation in a syringe. For the test injection, 1 ml of liposomal bupivacaine was diluted with 4 ml of preservative-free normal (0.9%) saline to create a total solution of 5 ml (13.3 mg of bupivacaine). For the third injection, 8 ml of liposomal bupivacaine was diluted with 12 ml of preservative-free normal (0.9%) saline to create a total solution of 20 ml (104 mg of bupivacaine).

CLINICAL RESPONSE

After the test injection, patient developed ptosis and miosis; this was less prominent than the findings seen immediately after prior stellate ganglion blockade. Patient reported recurrence of pain to peak intensity by Day 7, which was longer effect than previous stellate ganglion blockades. The patient reported an episode of aura, which consisted of visual scintillations on Day 2 that lasted for 6 h and resolved after sleeping. After the second injection, patient developed prominent ptosis and miosis with gradual resolution. Patient was pain free for 14 days following the stellate ganglion blockade. Patient reported recurrence of pain on Day 15 with return to peak intensity by Day 17, which was three folds longer duration of effect than previous stellate ganglion blocks using bupivacaine hydrochloride. She reported an episode of aura which consisted of visual scintillations on Day 2, which lasted for five days and resolved spontaneously. Patient was pain free for 27 days following the third stellate ganglion blockade. Patient reported recurrence of pain on Day 27 with return to peak intensity by Day 28, which was longer than the duration of effect than previous stellate ganglion blocks using lower dose of liposomal bupivacaine. She reported miosis immediately post procedure, which lasted for seven days and resolved spontaneously.

DISCUSSION

We observed a sustained pain relief with stellate ganglion blockade using liposomal bupivacaine injection with a clear difference in duration of action compared with bupivacaine hydrochloride. Bupivacaine is encapsulated in a liposomal formulation as phosphate salt, but concentration is expressed as bupivacaine free base. Approximately, 40 mg of bupivacaine base in the liposomal formulation is equivalent in strength to 45 mg of bupivacaine HCl [7]. On October 28, 2011, FDA approved EXPAREL, a bupivacaine liposome injectable suspension with the following statement: EXPAREL is a liposome injection of bupivacaine, an amide-type local anesthetic, indicated for administration into the surgical site to produce postsurgical analgesia. The efficacy of EXPAREL was compared with placebo in two multicenter, randomized double-blinded clinical trials [8, 9]. One trial evaluated the treatments in patients undergoing bunionectomy [8]; the other trial evaluated the treatments in patients undergoing hemorrhoidectomy [9]. EXPAREL has not been demonstrated to be safe and effective in other procedures. A meta-analysis pooling efficacy data from ten randomized, double-blind studies reported that cumulative pain intensity scores through 72 h were lower in 823 patients who were administered liposome bupivacaine (66–0.532 mg) compared with 446 patients who received bupivacaine HCl (dose: 75–200 mg) and 190 who received placebo [10].

Injection of liposomal bupivacaine for local nerve block requires additional data. In a porcine model, 4-ml liposomal bupivacaine 1.3% injected either perineurally or intraneurally extrafascicularly provided sensory blockade and did not reduce the nerve fiber density or myelin width of sciatic nerves [11]. Bilateral single-injection femoral nerve blocks were administered in 14 healthy volunteers using liposomal bupivacaine (0–80 mg). Peak effects occurred within 24 h after block administration in 75% of cases, and block duration usually lasted much longer for bupivacaine doses >40 mg [12], In another study,30 volunteers were randomized to receive liposome bupivacaine 89, 155, or 266 mg, or bupivacaine HCl 50 mg in a double-blind fashion administered as epidural injection [13]. Epidurally administered liposome bupivacaine 266 mg resulted in a longer duration of sensory blockade than liposome bupivacaine 89 or 155 mg or bupivacaine HCl 50 mg. In another retrospective study, multilevel intercostal nerve blocks using liposomal bupivacaine (1.3% liposomal bupivacaine diluted in 30-cc normal saline, total bupivacaine dose 4-mg/kg body weight) injected during open thoracotomy provided significantly better pain control in postoperative Days 1 and 3, compared with epidural analgesia [14].

We provide preliminary evidence to support using liposomal bupivacaine for sustained stellate ganglion blockade. The cost of liposomal bupivacaine [average wholesale price (AWP) 20-ml vial – $285] is higher compared with bupivacaine HCl (AWP $1–$3 per vial). Therefore, additional data are required to support the use of liposomal bupivacaine as first line agent for stellate ganglion blockade.