Case Report Treatment of Digital Ischemia with Liposomal ...

Case ReportTreatment of Digital Ischemia with Liposomal Bupivacaine

José Raul Soberón,1 Scott F. Duncan,2 and W. Charles Sternbergh3

1 Department of Anesthesiology, Ochsner Clinic Foundation, 1514 Jefferson Highway, New Orleans, LA 70121, USA2Department of Orthopedic Surgery, Ochsner Clinic Foundation, 1514 Jefferson Highway, New Orleans, LA 70121, USA3Vascular and Endovascular Surgery, Ochsner Clinic Foundation, 1514 Jefferson Highway, New Orleans, LA 70121, USA

Correspondence should be addressed to Jose Raul Soberon; [email protected]

Received 29 October 2013; Accepted 15 December 2013; Published 5 February 2014

Academic Editors: U. Deveci, A. Han, and J. Malek

Copyright © 2014 Jose Raul Soberon et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Objective. This report describes a case in which the off-label use of liposomal bupivacaine (Exparel) in a peripheral nerve blockresulted in marked improvement of a patient’s vasoocclusive symptoms. The vasodilating and analgesic properties of liposomalbupivacaine in patients with ischemic symptoms are unknown, but our clinical experience suggests a role in the management ofpatients suffering from vasoocclusive disease. Case Report. A 45-year-old African American female was admitted to the hospitalwith severe digital ischemic pain. She was not a candidate for any vascular surgical or procedural interventions. Two continuoussupraclavicular nerve blocks were placed with modest clinical improvement. These effects were also short-lived, with the benefitsresolving after the discontinuation of the peripheral nerve blocks. She continued to report severe pain and was on multipleanticoagulant medications, so a decision was made to perform an axillary nerve block using liposomal bupivacaine (Exparel) giventhe compressibility of the site as well as the superficial nature of the target structures. Conclusions. This case report describes thesuccessful off-label usage of liposomal bupivacaine (Exparel) in a patient with digital ischemia. Liposomal bupivacaine (Exparel) iscurrently FDA approved only for wound infiltration use at this time.

1. Introduction

Chemical sympathectomy from peripheral nerve blockadeis well known and especially beneficial in vascular surgery[1]. Limited data are available regarding chemical sympa-thectomy in patients with digital ischemic pain and vas-culopathy. Patients with these conditions, especially thosewith ischemic pain secondary to autoimmune disorders,benefit from chemical and surgical sympathectomy [2, 3].The benefits of surgical sympathectomy often persist for yearsafter the surgical procedure [3].

Exparel is a liposomal bupivacaine formulation that iscurrently FDA approved only for wound infiltration use.While this novel anesthetic is most commonly used duringbunion and hemorrhoid surgery, it is also used in a numberof other colorectal and orthopedic procedures and is gainingpopularity in other surgical specialties [4, 5]. Its vasodilatoryproperties are unknown at this time.

2. Case Report

Written informed consent was obtained from the patientafter a lengthy discussion of the known and potential risksand benefits of the block procedure, and all questions wereanswered. Witnessed verbal consent was obtained from thepatient prior to the preparation of this case report. Addi-tionally, the Ochsner Clinic Foundation Institutional ReviewBoard was contacted and determined that IRB approval wasnot necessary for the submission of this case report.

A 45-year-old African American female presented witha two-week history of severe pain in the 4th and 5th digitsof her right hand. Her past medical history was significantfor poorly controlled type I diabetes, hypertension, peripheralvascular disease, and opiate dependence. Imaging studies ofthe extremity revealed diminished flow and occlusion of thedistal ulnar artery. Her physical exam revealed cyanosis of the4th and 5th digits with limited hand movement secondary todiscomfort.

Hindawi Publishing CorporationCase Reports in AnesthesiologyVolume 2014, Article ID 853243, 4 pageshttp://dx.doi.org/10.1155/2014/853243

2 Case Reports in Anesthesiology

Thevascular surgery teampostulated that her ulnar arterywas injured during attempts at intravascular catheter place-ment during a recent admission for diabetic ketoacidosis.After angiography, the vascular surgeons determined thatshe was not a candidate for direct revascularization withintra-arterial thrombolysis or operative intervention. Thepatient was not offered an amputation by the surgical teamat this time because the ischemic regions of her hand hadnot fully demarcated and to allow the possibility of healingif nonsurgical interventions were successful. Additionally,she initially declined an amputation when the possibilityof one was discussed during her hospitalization. A heparininfusion and oral aspirin were initiated for anticoagula-tion therapy. Anesthesiology was then contacted to placea nerve block to assist with pain control and provide achemical sympathectomy. A supraclavicular nerve catheterwas placed under Ultrasound guidance, and her pain andclinical symptomsmodestly improved over the next two days.Her nerve catheter was removed and she was dischargedhome. Aspirin and clopidogrel were prescribed for outpatientuse.

However, she was readmitted to the hospital two dayslater complaining of continued pain in her hand. Clinicalexamination showed that her condition had regressed towhatit was during her initial presentation, with increased cyanosiswhen compared to prior to discharge. In addition to aspirinand clopidogrel, enoxaparin and coumadin were added toher anticoagulation regimen, and the anesthesia team wasconsulted to place a second nerve block.

A supraclavicular nerve catheter was placed but becamedislodged less than 48 hours after its insertion. The patientwas scheduled for a repeat block procedure with the expec-tation that she would be discharged home soon afterwards ifher pain and symptoms improved. She was determined not tobe a suitable candidate for an outpatient perineural catheter.

An ultrasound-guided Axillary block was performedusing 1.3% liposomal bupivacaine (Exparel), with 3mLinjected incrementally around the musculocutaneous, radial,median, and ulnar nerves. A total of 12mL of liposomalbupivacaine was used, corresponding to a total dose of159.6mg. A repeat supraclavicular catheter was not per-formed because of the patient’s anticoagulated state and thepossibility of hospital discharge if her symptoms improved.She was monitored in the block area 30 minutes after theprocedure and placed on continuous telemetry monitoringfor the remainder of her hospital stay.

She continued to report high pain scores in spite ofappearing more comfortable following the procedure. Thenext day, the vascular surgeon noted an improvement in herphysical examination, with normal color in the 5th digit andup to the dorsal aspect of the distal 1/3 and plantar to theproximal 1/3 of the 4th digit. She also had increased gripstrength and hand movement.

These clinical improvements were markedly better thanwhat she experienced with the previous supraclavicularblocks, and she was discharged home. She did not experienceany signs or symptoms of local anesthetic toxicity at any pointduring her hospitalization, and she denied them on dailytelephone followup for five days.

Photoplethysmography (PPG) flow studies provide aqualitative measure of digital arterial perfusion bymeasuringthe digital artery pulsatility. Progressive reduction in digitalarterial flow creates damping of the waveform. A “flatline”suggests very poor arterial flow. These PPG studies wereperformed during her hospital admissions, and the results areillustrated in Figure 1.

She demonstrated no pulsatility in the affected 4th and5th digits prior to treatment, consistent with the clinical pre-sentation. Although the patient’s pain and clinical symptomsimproved while receiving a perineural infusion of local anes-thetics, these benefits did not persist after discontinuation ofher peripheral nerve catheter, and no improvements in digitalblood flow were seen in PPG studies. Moreover, increasedflow in her 4th and 5th digits was observed on the PPG studiesone week after the liposomal bupivacaine block.

Unfortunately, the patient’s ischemic vasculopathy wors-ened over the subsequent six weeks, and her 4th fingerbecame gangrenous. She was scheduled for a 4th digit ampu-tation and surgical sympathectomy of the 4th and 5th digitsas an outpatient. During her surgical procedure, however,it was found that her common digital arteries were clotted.A surgical sympathectomy was nonetheless performed eventhough the efficacy of doing this procedure in vessels thatare already clotted is unknown. The patient underwent anamputation at the level of the proximal interphalangeal jointto remove the gangrenous digit. Her amputation site healedwithout complication, and she has had no other ischemicissues with the remaining digits. On followup, she reportedbetter pain control and use of the hand compared to prior tosurgery.

3. Discussion

Our decision to use an off-label medication was based onmultiple factors, with patient safety being at the forefront.Our indication for a block in this scenario, unlikemost of ourroutine cases, was not postoperative pain control, avoidanceof a general anesthetic, orminimization of opioid-related sideeffects, but a last-effort attempt at preserving the patient’sdigits.

We believe that our clinical decisions, albeit controversial,were based on careful consideration of the benefits and risks,specifically improving blood flow in an attempt to salvage atleast part of a limb against the possibility of nerve injury, localanesthetic toxicity, or other potential (currently unknown)risks associated with liposomal bupivacaine. Given her his-tory of opioid dependence, her pain was difficult to controlwith oral and intravenous analgesics. At the time of theliposomal bupivacaine block, the patient was on multipleanticoagulant medications, each acting on a different facetof the coagulation process. An axillary block was deemedsafer than a repeat supraclavicular block on an anticoagulatedpatient, because of ease of block performance and com-pressibility of the site should bleeding occur. Furthermore,the block was performed by a Fellowship trained regionalanesthesiologist (J. R. Soberon) with extensive experience inUltrasound-guided peripheral nerve blocks. A strict in-plane

Case Reports in Anesthesiology 3

Before initial Supraclavicular blockOne week after exparel

(liposomal bupivacaine) block

Before second Supraclavicular block(four days after discontinuation of

initial perineural infusion)

(R) 1st digit (R) 1st digit (R) 1st digit

(R) 4th digit (R) 4th digit (R) 4th digit

(R) 5th digit (R) 5th digit (R) 5th digit

Figure 1: Results from photoplethysmography (PPG) studies obtained throughout the patient’s hospitalizations. Of particular interest is thesustained blood flow seen in the 4th and 5th digits one week after her liposomal bupivacaine (Exparel) block. The 1st digit was nonischemicand included as a control.

techniquewas used to visualize the needle at all times to avoidvascular trespass or intraneural injection. Meticulous andfrequent aspiration were negative for blood during the blockprocedure. Avoiding a block altogether would have likely ledto worsening ischemia and the loss of the 5th digit, as well asa prolonged hospitalization for pain control purposes.

Exparel is a liposomal bupivacaine formulation that iscurrently FDA approved only for wound infiltration use,although FDA trials for perineural use approval are currentlyunderway. Its vasodilatory properties are unknown at thistime.

Patients with vaso-occlusive disorders benefit fromperipheral nerve blocks because of their vasodilating andanalgesic effects. In addition to chemical sympathectomy,surgical sympathectomy may be attempted to increase bloodflow to the digits [2, 3]. The most common surgical approachinvolves identifying the common digital arteries and remov-ing the adventitia from the vessels over a 1- to 2- centimetersegment. This removal of the adventitia disrupts the zonewhere the nerves lie, allowing for subsequent vasodilationand potentially increased blood flow.

It is unclear if improved control of the patient’s medicalissues, as well as increased adherence to therapy and medicalrecommendations, would have yielded a better outcome. Ourpatient was spared amputation of the 5th digit, which wasalso ischemic and cyanotic during her presentation. OurPPG results and clinical experience suggest that liposomal

bupivacaine may increase blood flow and assist with paincontrol in patients with digital ischemia. Further researchneeds to be performed to determine the safety and potentialrole of liposomal bupivacaine in peripheral nerve block use,particularly with regards to analgesic and vasodilating effectsin patients with ischemic symptoms.

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper. Dr. Soberon’s insti-tution received a research grant from Pacira Pharmaceuti-cals, Inc. (Parsippany, NJ) several months after the describedevents occurred. Drs. Duncan and Sternbergh have nofinancial disclosures.

Acknowledgments

The authors would like to thank Armin Schubert, M.D., andBobby Nossaman, M.D., of the Ochsner Clinic FoundationDepartment of Anesthesiology as well as Kathleen McFad-den, M.A., from Ochsner Clinic Foundation PublishingServices for proofreading and editing this paper. The authorsare also grateful to Barbara Siede, M.S., from Ochsner ClinicFoundationMedical Illustration Services for her assistance inthe labeling of their image.

4 Case Reports in Anesthesiology

References

[1] E. B. Malinzak and T. J. Gan, “Regional anesthesia for vascularaccess surgery,” Anesthesia and Analgesia, vol. 109, no. 3, pp.976–980, 2009.

[2] R. A. Greengrass, N. G. Feinglass, P. M.Murray, and S. D. Trigg,“Continuous regional anesthesia before surgical peripheralsympathectomy in a patient with severe digital necrosis asso-ciated with Raynaud’s phenomenon and scleroderma,” RegionalAnesthesia and Pain Medicine, vol. 28, no. 4, pp. 354–358, 2003.

[3] K. Murata, S. Omokawa, Y. Kobata, Y. Tanaka, H. Yajima, andS. Tamai, “Long-term follow-up of periarterial sympathectomyfor chronic digital ischaemia,” J Hand Surg Eur, vol. 37, no. 8, pp.788–793, 2012.

[4] K. Candiotti, “Liposomal bupivacaine: an innovative nonopioidlocal analgesic for the management of postsurgical pain,”Pharmacotherapy, vol. 32, supplement 9, pp. 19S–26S, 2012.

[5] Pacira Pharmaceuticals Inc, EXPAREL (Bupivacaine LiposomeInjectable Suspension) Prescribing Information, Pacira Pharma-ceuticals Inc, Parsippany, NJ, USA, 2011.

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