OPIOID-SPARING ANALGESIA:Why 24 Hours Isn’t Enough

Brian Vaughan, MDDirector, Acute Pain Service

The Christ Hospital, Cincinnati, OH

33

DISCLAIMER

Halyard Health is sponsoring this presentation and I am being compensated by Halyard Health to make this presentation. The presentation has been reviewed by Halyard Health and is consistent with Halyard Health’s product labeling.

The information provided in this presentation is intended for training and educational purposes only and represents my technique, including catheter placement. Techniques can vary depending on the individual expertise, experience and school-of-thought of the physician using the ON-Q* Pain Relief System. Always refer to Halyard Health’s Instructions for Use and the drug manufacturer’s prescribing information when placing Halyard Health’s products and administering any drugs through them.

This presentation is not intended as a recommendation to purchase or use Halyard Health products.

44

OBJECTIVES

• Anesthesia Trends: Shift of Care and Impact on Practice

• Opioid Epidemic

• Multimodal Pain Protocols

• Clinical Literature Review– Continuous vs Single Shot PNB vs Liposomal Bupivacaine

• Case Study: The Christ Hospital

ANESTHESIA TRENDS

66

OLD PARADIGM

STEP

1 PUT PATIENT TO SLEEP

WAKE PATIENT UP3

REPEAT STEP 14

2 KEEP PATIENT ALIVE

77

NEW PARADIGM

• Complication rates• Functional outcomes• Chronic pain and pain syndromes• Long-term survival

START WITH...

OLD PARADIGM

IMPACT ON...

88

DOES ANESTHESIA MATTER?

• Complication Rates– The Effects of Intraoperative Hypothermia on Surgical Site Infection: An Analysis of 524 Trauma Laparotomies

Seamon, et al. Ann Surg. 2012; 255: 789

• Functional Outcomes– Effect of Femoral Nerve Catheter Infusion on ROM and Need for Manipulation Following TKA

Talmo, et al. AAOS Annual Meeting 2012; 195

– Preincisional Paravertebral Block Reduces the Prevalence of Chronic Pain after Breast SurgeryKairaluoma, et al. Anesth Analg. 2006; 103(3): 703

• Cancer Recurrence– Surgery for Cancer: Does Anesthesia Matter?

Bovill. Anesth Analg. 2010; 110: 1524

– Can Anesthetic Technique for Primary Breast Cancer Surgery Affect Recurrence or Metastasis? Exadaktylos, et al. Anesthesiology. 2006; 105: 660

99

POST-OP CHRONIC PAIN

• Lower extremity arthroplasty – Incidence up to 53% – knee > hip

Liu, et al. RAPM. 2012; 37: 415

• Post-mastectomy pain syndrome– Incidence 10-50%

Gartner, et al. JAMA. 2009; 302: 1985; Kairaluoma, et al. Anesth Analg. 2006; 103:703

• Post-thoracotomy pain syndrome– Incidence 30-50%

Karmakar, et al. Thorac Surg Clinic. 2004; 14: 345; Katz, et al. Clin J Pain. 1996; 12: 50

1010

PERI-OP IMMUNE SUPPRESSION

Source: Gottschalk, et al. Anesth Analg. 2010; 110(6): 1636

1111

PRACTICEof Medicine

BUSINESSof Medicine

Increase REVENUE

Reduce COSTS

Increase QUALITY

PRACTICE vs. BUSINESS of MEDICINE

OPIOID EPIDEMIC

1313

WHY NOT MOREPHINE?

• Sedation• Delirium• Respiratory compromise• Constipation• Prolonged ileus• Urinary retention• Itching• Nausea/vomiting

1414

NARCOTICS: UNINTENDED CONSEQUENCES

• Monitoring Costs– Pulse oximetry– End-tidal CO2

• Staffing time and costs• Addiction/Dependence• Cancer Recurrence?

1515

OPIOID ADDICTION CAN HAPPEN QUICKLY

DEPENDENCY CAN BEGIN WITHIN JUST 3 DAYS OF INITIAL OPIOID USE 1

As many as 1 in 5 patients becomes a routine opioid user after 10 DAYSof narcotic analgesia 1

Even a 1-DAY opioid prescription may pose a 6% risk of long-term use 1

1616

Every opioid-related, in-hospital adverse event increases costs by an average of

Opioid side effects such as constipation can prolong postoperative length of stay

by an average of 1.4 days4

OPIOID OVERPRESCRIBING IS COMMON AND COSTLY

According to a 2017 study in JAMA, new persistent opioid use should be considered one of the most common complications after elective surgery.5

of colectomy patients become newly persistent opioid users after surgery5

Based on prescription data, over

patients may become persistent opioid users every year following elective, ambulatory surgery5

2,3

MULTIMODAL PAIN PROTOCOLS

1818

SOURCES OF PAIN

Tissue Damage: Cutaneous, Visceral

Nerve Injury (Neuropathic)

Muscle Spasm Inflammation

1919

ANTERIOR HIP-HANA® TABLE

2020

ANTERIOR HIP-HANA® TABLE

2121

Pre-EmptiveAnalgesia

Intra-OpAnalgesia

Post-Op Analgesia(1st 24 hours)

Post-Op Analgesia(After 24 Hours)

At Home:• Voltaren 100mg po evening

before surgery

• Pregabalin 75mg po BID for 3 days prior to surgery

PLUS

In pre-op holding per surgeon order set:• Pregabalin 75mg po

• Oxycodone SR 10mg po

• Lidocaine bolus 100mg IV

• Lidocaine infusion at 1.5mg/kg/hour-discontinue at closure of fascia

• Ketamine 1-2mg/kg bolus at induction

• Acetaminophen IV 1g (or weight-based dose)

• cTAP block prior to emergence

• Bolus injection Ropiv. 0.25-0.5% 30 ml per side

• cTAP block• Ropiv 0.2% infusion titrating

to patient comfort

• Ketorolac 15-30mg IV q6

• Acetaminophen 1g IV q8

• Morphine or hydromorphone PCA

• Pregabalin 75mg po BID

• cTAP block• Ropiv 0.2% infusion

titrating to patient comfort

• Remove cTAP with return of bowel function on POD 6

• Patient may go home withcTAP if desired.

• PCA d/c POD 2

• Oxycodone 5-10mg po q4 prn

• Pregabalin 75mg po BID

• Ibuprofen 800mg po TID

• Acetaminophen 1g po QID

MULTIMODAL EXAMPLE

* Based on Colectomy procedure

2222

IMPLEMENTING A MULTIMODAL APPROACH CAN HELP REDUCE POSTOPERATIVE OPIOID USETREATMENT GOALS

Reduce opioid use

Provide pain relief for days,not just hours

Reduce complicationsdue to opioid use

Offer customizable control with ability to turn analgesia on and off

Improve cost-effectiveness by limiting factors like length of stay

Satisfy patients by getting them back to normal faster

2323

BLOCKS PERFORMED AT TCH

TAP Paravertebral Interscalene

Supraclavicular Infraclavicular Axillary

Femoral/Adductor Sciatic Fascia Iliaca

Lumbar Plexus Popliteal Saphenous

CLINICAL LITERATURE REVIEWContinuous vs. Single shot vs. Liposomal Bupivacaine

2525

A MULTICENTER, RANDOMIZED, TRIPLE-MASKED, PLACEBO-CONTROLLED TRIAL OF THE EFFECT OF AMBULATORY CONTINUOUS FEMORAL NERVE BLOCKS ON DISCHARGE-READINESS FOLLOWING TOTAL KNEE ARTHOPLASTY IN PATIENTS ON GENERAL ORTHOPAEDIC WARDS

• Continuous vs. single injection femoral block

• Discharge criteria:– Adequate analgesia– Freedom from IV narcotics– Sufficient ambulation ability to allow home discharge (≥ 30m)

• Time to meet all 3 criteria 47 vs. 62 hours (p=0.028)

Ilfeld, et al. Pain. 2010; 150: 477

2626

WILL THE REAL BENEFITS OF SINGLE-SHOT INTERSCALENE BLOCK PLEASE STAND UP? A SYSTEMATIC REVIEW AND META-ANALYSIS

• Single injection block:– Effective for only 6-8 hours– Decreased opioid use over first 12 hours– Reduced PONV for 24 hours

• May have rebound pain at 24 hours– Total opioid use no different over 48 hours

Abdallah, F. W., et. al. Anesth Analg. 2015; 120(5): 1114

2727

PERSISTENT POSTMASTECTOMY PAIN AND PAIN-RELATED PHYSICAL AND EMOTIONAL FUNCTIONING WITH AND WITHOUT AND CONTINUOUS PARAVERTEBRAL NERVE BLOCK: A PROPSECTIVE 1-YEAR FOLLOW-UP ASSESSMENT OF A RANDOMIZED, TRIPLE-MASKED, PLACEBO-CONTROLLED STUDY

• Chronic pain post-mastectomy seen in 30-73% of patients

• 3 day continuous vs. single injection PVB for mastectomy

• Less pain and less pain-related physical and emotion dysfunction at 1 year for those receiving continuous block (13% vs. 47%)

Ilfeld, et al. Ann Surg Oncol. 2015; 22: 2017

2828

LIPOSOMAL BUPIVACAINE VERSUS INDWELLING INTERSCALENE NERVE BLOCK FOR POSTOPERATIVE PAIN CONTROL IN SHOULDER ARTHROPLASTY: A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL.

• Continuous interscalene block vs. liposomal bupivacaine periarticular injection

Abildgaard, et al. J Shoulder Elbow Surg. 2017; 26(7): 1175

POSTOPERATIVE OPIATE USAGE

0

20

40

60

80

OR PACU POD 0 POD 1 POD 2

ORA

L M

SO4

EQ

UIV

ALEN

TS

Chart Title LB ISC

* * *

PACU POD 0 POD 1 POD 2OR

TOTAL OME: EXPAREL = 189.6 | ISC = 91.7 p = 0.0001

0

2

4

6

8

PACU POD 0 POD 1 POD 2

VAS

PAIN

SCO

REChart TitleLB ISC

PACU POD 0 POD 1 POD 2

POSTOPERATIVE PAIN LEVEL

**

• ISC block:- Decreased

narcotic use- Improved

pain scores

2929

ADDITION OF LIPOSOME BUPIVACAINE TO BUPIVACAINE HCL VERSUS BUPIVACAINE HCL ALONE FOR INTERSCALENE BRACHIAL PLEXUS BLOCK IN PATIENTS HAVING MAJOR SHOULDER SURGERY

• No difference in opioid consumption between the 2 groups

• Minimal difference in pain score

• Clinically relevant comparison? (7.5mg +133mg vs. only 37.5mg)

Vandepitte, C., et. al. Reg Anesth and Pain Med. 2017; 42(3): 334

POSTOPERATIVE OPIOID CONSUMPTION (mEq)

0

1

2

3

4

POD 1 POD 2 POD 3 POD 4 POD 7ORA

L EQ

UIV

ALEN

TS (t

ram

adol

) Chart TitleLB + Std Bupi Std Bupi

TOTAL OME: LB + Std Bupi = 10.4 | Std Bupi = 10.5

Unadj P 0.8 0.3 0.5 0.9 0.9

3030

INTERSCALENE COMPLICATIONS

• Phrenic nerve involvement– Bupivacaine > Ropivacaine– Respiratory insufficiency- caution in COPD

• Recurrent laryngeal nerve paralysis– Caution in patients with pre-existing vocal cord lesions– During infusion <5%

• Horner’s syndrome– Benign/cosmetic– Must pre-educate patients

Side Effects

3131

ANALGESIA AND FUNCTIONAL OUTCOME AFTER TOTAL KNEE ARTHROPLASTY: PERIARTICULAR INFILTRATION VS CONTINUOUS FEMORAL NERVE BLOCK

• Prospective, randomized, double-blinded

• Femoral block group:– Decrease narcotic use POD 1-2– More time walking POD 1-2– No difference in walk test POD 1-3– Better walk test at 6 weeks

Carli, F., et. al. British Journal of Anaesthesia. 2010; 105(2): 185

3232

RETROSPECTIVE, CONTROLLED EVALUATION COMPARING PAIN MANAGEMENT UTILIZING A BILATERAL CONTINUOUS TAP BLOCK TO PAIN MANAGEMENT USING BILATERAL LIPOSOMAL BUPIVACAINE TAP BLOCKS FOLLOWING SPINE SURGICAL PROCEDURES WITH AN ANTERIOR APPROACH

• Continuous TAP blocks vs. liposomal bupivacaine

• Continuous TAP blocks:– Over 30% less narcotic used– Faster return of bowel function– Decreased length of stay by 1 day

• Hospital savings of $800-$1000 due to earlier discharge

Vaughan B. Poster #262. ASRA 2015

3333

PAI/LAI COMPLICATIONS

• Ventricular tachycardia• Hypertensive crisis• Motor weakness – sciatic• Falls• Local anesthetic systemic toxicity (LAST)

3434

FOOD FOR THOUGHT….

• Local infiltration – 2nd most common cause of local anesthetic systemic toxicity

• Bupivacaine most commonly involved local anesthetic agent

LOCAL ANESTHETIC SYSTEMIC TOXICITY: A REVIEW OF RECENT CASE REPORTS AND REGISTRIESGittman and Barrington. RAPM. 2018; 43(2): 124

3535

FOOD FOR THOUGHT….

• FDA review of surveillance data, “identified 93 cases of LAST reported with Exparel and IR LA’s through July 26, 2016. Exparel use was reported in 36 cases...”

• Unanimous agreement that more studies need to be done • “Moreover, the sales data showed that in 2015, Exparel accounted for 4% of sales of single-ingredient

bupivacaine…”

FDA BRIEFING DOCUMENT: ANESTHETIC AND ANALGESIC DRUG PRODUCTS ADVISORY COMMITTEE MEETING (February 14 and 15, 2018)

• In accordance with recommendations made by an FDA advisory committee in February, the agency has determined that clinical trial data is not sufficient to support the general use of Exparel for regional nerve blocks for post-surgical analgesia other than shoulder surgery.

FDA IN BRIEF: FDA APPROVES NEW USE OF EXPAREL FOR NERVE BLOCK PAIN RELIEF FOLLOWING SHOULDER SURGERIES(April 6, 2018)

3636

WHY CATHETERS?

• Consistent, predictable effects

• Efficacy does not wane with time

• Customizable– Titratable– Long, flexible range of duration– Ability to discontinue when desired

• Well studied

In theory there is no difference between theory and practice. In practice

there is.

– YOGI BERRA

CASE STUDY: THE CHRIST HOSPITAL (TCH)

3939

THE REAL WORLD

• 550-bed private community hospital• No anesthesia residents• Average Length of Stay (LOS) for total knees and hips:

1.7

2.8

3.9

0 1 2 3 4

2017

6-MO POST BLOCK PRGM

PRE-BLOCK PRGM

DAYS

LENGTH OF STAY (DAYS)

4040

HCAHPS: THE CHRIST HOSPITAL

Source: HCAHPS scores - https://data.medicare.gov/Hospital-Compare/Patient-survey-HCAHPS-National/99ue-w85f; https://data.medicare.gov/Hospital-Compare/Patient-survey-HCAHPS-State/84jm-wiui; Data on file, The Christ Hospital

Patients who reported that their pain was “Always” well controlled

CHRIST HOSPITAL

OHIO AVERAGE

NATIONAL AVERAGE

75% 71% 71%

4141

RAISING THE BAR

Is your pain always well controlled?

Source: HCAHPS scores - https://data.medicare.gov/Hospital-Compare/Patient-survey-HCAHPS-National/99ue-w85f; https://data.medicare.gov/Hospital-Compare/Patient-survey-HCAHPS-State/84jm-wiui; Data on file, The Christ Hospital

National Average 71%

Ohio Average 71%

TCH: All Floors 75%

TCH: 5 South (General Surgery) 82%

TCH: 2 and 3 South (Orthopedics) 85%

The Christ Hospital

4242

TCH TOTAL JOINT VOLUMES

• Block program begun in FY 2006– Two total joint

surgeons– Approximately 400-500

total joint cases

500

2,3022,780

3,261

3,835

FY 2006 FY 2014 FY 2015 FY 2016 FY 2017

Number of Cases

Over 20% compounded annual growth

4343

TCH JOINT & SPINE CENTER

PROGRAM FY 2015 FY 2017 MARKET POSITION

Joints 19.6% 29.3% FIRSTOrtho 15.4% 19.4% FIRSTSpine 23.98% 28.4% FIRST

4444

ON-Q* PAIN RELIEF SYSTEM FOR CPNB

4545

ON-Q* PUMP CONSIDERATIONS

• User-friendly, especially for patients• Reliable• Patient autonomy with Select-A-Flow*• Better sleep, patient does not need to awaken to give a bolus• Training and inservicing• Capability to fill to 550cc, at 8cc/hr = 69 hours• Dual Pump fills to 750cc, max 7cc/hr per side

4646

ON-Q* OFFERS EXTENDED RELIEF FOR UP TO 5 DAYS, REDUCING THE NEED FOR OPIOIDS FROM DAY 1

44 clinical trials have demonstrated significant reduction of opioid use with ON-Q*42

ON-Q* has 20 years of innovation, 100 clinical studies, and has been used by over 6.4 million patients42

ON-Q* delivers continuous relief andnon-opioid pain control for up to 5 days16,39

39-41

4747

QUESTIONS?

?

4848

REFERENCES1. Centers for Disease Control and Prevention (CDC). Characteristics of initial prescription episodes and likelihood of long-term opioid use—United States, 2006-2015. https://www.cdc.gov/mmwr/volumes/66/wr/mm6610a1.htm. Accessed February 7, 2018.2. Oderda GM, Gan TJ, Johnson BH, Robinson SB. Effect of opioid-related adverse events on outcomes in selected surgical patients. J Pain Palliat Care Pharmacother. 2013;27:62-70. 3. Kessler ER, Shah M, Gruschkus SK, Raju A. Cost and quality implications of opioid-based postsurgical pain control using administrative claims data from a large health system: opioid-related adverse events and their impact on clinical and economic outcomes.

Pharmacotherapy. 2013;33(4):383-391. 4. Pizzi LT, Toner R, Foley K, et al. Relationship between potential opioid-related adverse effects and hospital length of stay in patients receiving opioids after orthopedic surgery. Pharmacotherapy. 2012;32:502-514. 5. Brummett CM, Waljee JF, Goesling J, et al. New persistent opioid use after minor and major surgical procedures in US adults. JAMA Surg. 2017;152(6):e170504. 6. Sun EC, Darnall BD, Baker LC, Mackey S. Incidence of and risk factors for chronic opioid use among opioid-naïve patients in the postoperative period. JAMA Intern Med. 2016;176(9):1286-1293.7. Benyamin R, Trescot AM, Datta S, et al. Opioid complications and side effects. Pain Physician. 2008;11:s105-s120.8. Forastiere E, Sofra M, Giannarelli D, Fabrizi L, Simone G. Effectiveness of continuous wound infusion of 0.5% ropivacaine by ON-Q pain relief system for postoperative pain management after open nephrectomy. Br J Anaesth. 2008;101(6):841-847. 9. Parvizi J, Miller AG, Gandhi K. Multimodal pain management after total joint arthroplasty. J Bone Joint Surg Am. 2011;93(11):1075-1184. 10. Webb C, Mariano E. Best multimodal analgesic protocol for total knee arthroplasty. Pain Management. 2015;5(3):185-196.11. Dulaney-Cripe E, Hadaway S, Bauman R, Trame C, Smith C, Sillaman B, et al. A continuous infusion fascia iliaca compartment block in hip fracture patients: a pilot study. Journal of Clinical Medicine Research. 2012;4(1):45-8. 12. Foss NB, Kristensen BB, Bundgaard M, Bak M, Heiring C, Virkelyst C, et al. Fascia iliaca compartment blockade for acute pain control in hip fracture patients. Anesthesiology. 2007Apr;106(4):773-8. 13. Mouzopoulos G, Vasiliadis G, Lasanianos N, Nikolaras G, Morakis E, Kaminaris M. Fascia iliaca block prophylaxis for hip fracture patients at risk for delirium: a randomized placebo-controlled study. Journal of the American Geriatrics Society. 2001May;49(5):516-22. 14. Kinjo S, Lim E, Sands LP, Bozic KJ, Leung JM. Does using a femoral nerve block for total knee replacement decrease postoperative delirium? BMC Anesthesiology. 2012Mar10;12(4). 15. Del Rosario E, Esteve N, Sernandez MJ, Batet C, Aguilar JL. Does femoral nerve analgesia impact the development of postoperative delirium in the elderly? A retrospective investigation. Acute Pain. 2008Jun;10(2):59-64. 16. IFU - The ON-Q* Pain Relief System. Instructions for use. 17. Auyong DB, Allen CJ, Pahang JA, Clabeaux JJ, MacDonald KM, Hanson NA. Reduced length of hospitalization in primary total knee arthroplasty patients using an updated enhanced recovery after orthopedic surgery (ERAS) pathway. J Arthroplasty. 2015;30(10):1705-1709. 18. Bingham AE, Fu R, Horn JL, Abrahams MS. Continuous peripheral nerve block compared with single-injection peripheral nerve block: a systematic review and meta analysis of randomized controlled trials. Reg Anesth Pain Med. 2012;37(6):583-594. 19. Dine A. Evidence based outcomes review. Continuing review and evaluation for I-Flow Corporation. July 2012. 20. Goyal N, McKenzie J, Sharkey PF, Parvizi J, Hozack WJ, Austin MS. The 2012 Chitranjan Ranawat award: intraarticular analgesia after TKA reduces pain: a randomized, double-blinded, placebo-controlled, prospective study. Clin Orthop Relat Res. 2013;471(1):64-75. 21. Liu SS, Richman JM, Thirlby RC, Wu CL. Efficacy of continuous wound catheters delivering local anesthetic for postoperative analgesia: a quantitative and qualitative systematic review of randomized controlled trials. J Am Coll Surg. 2006;203(6):914-932. 22. American Academy of Orthopaedic Surgeons Information statement. Opioid use, misuse, and abuse in orthopaedic practice.

https://www.aaos.org/uploadedFiles/PreProduction/About/Opinion_Statements/advistmt/1045%20Opioid%20Use,%20Misuse,%20and%20Abuse%20in%20Practice.pdf. Published October 2015. Accessed February 14, 2018. 23. Aguirre J, Del Moral A, Cobo I, Borgeat A, Blumenthal S. The role of continuous peripheral nerve blocks. Anesthesiol Res Pract. 2012;2012:1-20. 24. Chelly JE, Ghisi D, Fanelli A. Continuous peripheral nerve blocks in acute pain management. Br J Anaesth. 2010;105(suppl 1):86-96. 25. Heller L, Kowalski AM, Wei C, Butler CE. Prospective, randomized, double-blind trial of local anesthetic infusion and intravenous narcotic patient-controlled anesthesia pump for pain management after free TRAM flap breast reconstruction. Plast Reconstr Surg.

2008;122(4):1010-1018. 26. The Joint Commission. Safe use of opioids in hospitals. Sentinel Event Alert. Issue 49, August 8, 2012. 27. Beaussier M, El’Ayoubi H, Schiffer E, et al. Continuous preperitoneal infusion of ropivacaine provides effective analgesia and accelerates recovery after colorectal surgery. Anesthesiology. 2007;107(3):461-468. 28. Bianconi M, Ferraro L, Traina GC, et al. Pharmacokinetics and efficacy of ropivacaine continuous wound instillation after joint replacement surgery. Br J Anaesth. 2003;91(6):830-835. 29. Capdevila X, Barthelet Y, Ryckwaert Y, Rubenovitch J, d’Athis F. Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation after major knee surgery. Anesthesiology. 1999;91(1):8-15. 30. Carli F, Clemente A, Asenjo JF, et al. Analgesia and functional outcome after total knee arthroplasty: periarticular infiltration vs continuous femoral nerve block. Br J Anaesth. 2010;105(2):185-195. 31. Dowling R, Thielmeier K, Ghaly A, Barber D, Boice T, Dine A. Improved pain control after cardiac surgery: results of a randomized, double-blind, clinical trial. J Thorac Cardiovasc Surg. 2003;126(5):1271-1278. 32. Ilfeld BM, Ball ST, Gearen PF, et al. Ambulatory continuous posterior lumbar plexus nerve blocks after hip arthroplasty: a dual-center, randomized, triple-masked, placebo controlled trial. Anesthesiology. 2008;109(3):491-501. 33. Mudumbai SC, Kim TE, Howard SK, et al. Continuous adductor canal blocks are superior to continuous femoral nerve blocks in promoting early ambulation after TKA. Clin Orthop Relat Res. 2014;472(5):1377-1383. 34. White PF, Rawal S, Latham P, Markowitz S, et al. Use of a continuous local anesthetic infusion for pain management after median sternotomy. Anesthesiology. 2003;99(4):918-923.35. Haslam L, Lansdown A, Lee J, Vyver MVD. Survey of current practices: peripheral nerve block utilization by ED physicians for treatment of pain in the hip fracture patient population. Canadian Geriatrics Journal. 2013;16(1).16-21.36. Zywiel MG, Hurley RT, Perruccio AV, Hancock-Howard RL, Coyte PC, Rampersaud YR. Health economic implications of periopoerative delirium in older patients after surgery for a fragility hip fracture. The Journal of Bone and Joint Surgery-American Volume.

2015May20;97(10):829-36. 37. Husain A, Lee GC. Establishing realistic patient expectations following total knee arthroplasty. J Am Acad Orthop Surg. 2015;23(12):707-713. 38. Kean J, Wigderowitz CA, Coventry DM. Continuous interscalene infusion and single injection using levobupivacaine for analgesia after surgery of the shoulder: a double blind, randomized controlled trial. J Bone Joint Surg [Br]. 2006;88-B:1173-1177.39. Abdallah FW, Halpern SH, Aoyama K, Brull R. Will the real benefits of single-shot interscalene block please stand up? A systematic review and meta-analysis. Anesth Analg. 2015;120(5):1114-1129.40. Golf M, Daniels SE, Onel E. A Phase III, randomized, placebo controlled trial of DepoFoam® bupivacaine (extended-release bupivacaine local analgesic) in bunionectomy. Adv Ther. 2011;28(9):776-788.41. Gorfine SR, Onel E, Patou G, Krivokapic ZV. Bupivacaine extended-release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, double-blind, placebo-controlled trial. Dis Colon Rectum. 2011

Dec;54(12):1552-9. 42. Data on file, Halyard Inc.

*Registered Trademark or Trademark of Halyard Health, Inc., or its affiliates.© 2018 HYH. All rights reserved COPY-02321 04/2018

There are inherent risks in all medical devices. Please refer to the product labeling for Indications, Cautions, and Warnings and Contraindications. Failure to follow the product labeling could directly impact patient safety. Physician is responsible for prescribing and administering medications per instructions provided by the

drug manufacturer. Refer to www.halyardhealth.com for product safety Technical Bulletins.