Redefining Local Anesthetic Redefining Local Anesthetic Infiltration TherapyInfiltration Therapy

Dr. Eugene ViscusiDr. Eugene ViscusiDepartment of AnesthesiologyDepartment of Anesthesiology

Jefferson Medical CollegeJefferson Medical College

Post-operative Pain Management:Traditional MethodsPost-operative Pain Management:Traditional Methods

Previous guidelines for post-operative analgesics were Previous guidelines for post-operative analgesics were “one size fits all” -- general recommendations for all “one size fits all” -- general recommendations for all surgical procedures based on pooled datasurgical procedures based on pooled data11

Anesthesiologist’s primary role in traditional settingAnesthesiologist’s primary role in traditional setting22

– Pre-operative preparationPre-operative preparation

– Provide optimal surgical conditionsProvide optimal surgical conditions

– Minimize pain immediately after surgeryMinimize pain immediately after surgery

1 1 Kehlet, Anesthesiology Clin N Am 2005 23:203-210Kehlet, Anesthesiology Clin N Am 2005 23:203-21022 White, Kehlet, et al, Anesthesia & Analgesia 2007 104:1380-1396 White, Kehlet, et al, Anesthesia & Analgesia 2007 104:1380-1396

Early Changes in Post-operative Pain ManagementEarly Changes in Post-operative Pain Management

Early changes in therapy included:Early changes in therapy included:– 1985 – Injection of bupivacaine following wound closure: patient 1985 – Injection of bupivacaine following wound closure: patient

free of pain for 11.5 hours free of pain for 11.5 hours11

– 1985 – First acute pain services established in the US and 1985 – First acute pain services established in the US and Germany Germany22

– 1990 – “Balanced” analgesia used to prevent post-operative pain 1990 – “Balanced” analgesia used to prevent post-operative pain in colorectal surgery in colorectal surgery33

– 1997 – Kehlet introduces multimodal concept for post-operative 1997 – Kehlet introduces multimodal concept for post-operative carecare44

Early clinical guidelines for post-operative painEarly clinical guidelines for post-operative pain– 2001 – US Veteran’s Health Administration2001 – US Veteran’s Health Administration55

1 1 Porter, Davis, An Royal Coll Surgeons Eng 1985; 67: 293-294.Porter, Davis, An Royal Coll Surgeons Eng 1985; 67: 293-294.22 Werner, Soholm, et al Anesth Analg 2002; 95:1361-72. Werner, Soholm, et al Anesth Analg 2002; 95:1361-72.3 3 Dahl, Rosenberg, et al, Br J Anes 1990; 64:581-520.Dahl, Rosenberg, et al, Br J Anes 1990; 64:581-520.44 Kehlet, Bri J Anes 1997;78:606-617. Kehlet, Bri J Anes 1997;78:606-617.55 www.oqp.med.va.gov/cpg/PAIN/PAIN_about.doc Accessed 10-116-08 www.oqp.med.va.gov/cpg/PAIN/PAIN_about.doc Accessed 10-116-08

Suboptimal Management of Post-operative Pain Suboptimal Management of Post-operative Pain

““Pain can be relieved effectively in 90% of patients, but is not relieved Pain can be relieved effectively in 90% of patients, but is not relieved effectively in 80% of patients.”effectively in 80% of patients.”

77

19

49

23

8

85

13

47

21 18

0102030405060708090

Any pain Slight pain Moderate pain Severe pain Extreme pain

19952003

Patient’s worst pain

Warfield CA, Kahn CH. Anesthesiology. 1995;83:1090-1904.Apfelbaum JL, Chen C, Mehta SS, Gan TJ. Anesth Analg. 2003;97:534-540.

Multimodal Management of Post-operative PainMultimodal Management of Post-operative Pain

Definition: Multimodal (balanced) anesthesia involves use Definition: Multimodal (balanced) anesthesia involves use of two or more analgesic agents with different of two or more analgesic agents with different mechanisms of action to achieve optimal analgesic effect mechanisms of action to achieve optimal analgesic effect by additive or synergistic effects.by additive or synergistic effects.1,21,2

1 1 White, Kehlet, et al, Anesthesia & Analgesia 2007 104:1380-1396White, Kehlet, et al, Anesthesia & Analgesia 2007 104:1380-139622 European Society of Regional Anaesthesia and Pain Therapy, European Society of Regional Anaesthesia and Pain Therapy, post-operative Pain post-operative Pain Management—Good Clinical Practice.Management—Good Clinical Practice.33 Umedaly, Umedaly, Multimodal Perioperative Pain Management and Multimodal Strategies to EnhanceMultimodal Perioperative Pain Management and Multimodal Strategies to Enhance Post Operative Outcomes. Post Operative Outcomes. http://www.phsa.ca/NR/rdonlyres/C879B328-3259-4753-BD39- http://www.phsa.ca/NR/rdonlyres/C879B328-3259-4753-BD39- 3E2C22408FCA/15620/9MultimodalPerioperativePainDrHamedUmedaly1.pdf. Accessed 3E2C22408FCA/15620/9MultimodalPerioperativePainDrHamedUmedaly1.pdf. Accessed 10-16-200810-16-2008

““Pain neurobiology is a complex of dynamic interrelated Pain neurobiology is a complex of dynamic interrelated systems. Unimodal analgesia cannot be sufficient to provide systems. Unimodal analgesia cannot be sufficient to provide optimal pain management. Additive and synergistic effects of optimal pain management. Additive and synergistic effects of multiple modes should improve outcomes.” Hamed multiple modes should improve outcomes.” Hamed Umedaly, MDUmedaly, MD33

Multimodal and Multi-Disciplinary ApproachMultimodal and Multi-Disciplinary Approach

Pre-operativePre-operativeinformation Attenuation Pain Exercise Enteral Growthinformation Attenuation Pain Exercise Enteral Growthand teaching of stress relief nutrition and teaching of stress relief nutrition factors factors

Controlling post-operative physiologyControlling post-operative physiology

Reduced morbidity and accelerated convalescenceReduced morbidity and accelerated convalescence

Adapted from graph: Kehlet, Bri J of Anes 1997; 78:614Adapted from graph: Kehlet, Bri J of Anes 1997; 78:614

Multimodal Management of Post-operative PainMultimodal Management of Post-operative Pain

Pre-operative Pre-operative issuesissues

– Risk Risk stratification stratification

– Anesthetic and Anesthetic and analgesic plananalgesic plan

Intra-operative issuesIntra-operative issues

– Local anesthesia Local anesthesia

• InfiltrationInfiltration

– Regional anesthesiaRegional anesthesia

• IV regional, IV regional, peripheral nerve peripheral nerve blocks, neuraxial blocks, neuraxial blocksblocks

– General anesthesiaGeneral anesthesia

Post-operative Post-operative issuesissues

– Pain Pain managementmanagement

– Nausea and Nausea and VomitingVomiting

– Ileus and Ileus and constipationconstipation

– PTPT

Benefits of Multimodal Pain Management Benefits of Multimodal Pain Management

BenefitsBenefits– Reduced morbidityReduced morbidity

– Enhanced post-operative recovery of organ functionsEnhanced post-operative recovery of organ functions

– Accelerated convalescenceAccelerated convalescence11

– Reduction of opioid useReduction of opioid use

– Reduced doses of each analgesicReduced doses of each analgesic

– Improved antinociception due to synergistic/additive effectsImproved antinociception due to synergistic/additive effects

– Reduction in severity of side effectsReduction in severity of side effects22

1 1 Kehlet, Bri J Anes 1997;78:606-617.Kehlet, Bri J Anes 1997;78:606-617.22 Umedaly, Umedaly, Multimodal Perioperative Pain Management and Multimodal Strategies to EnhanceMultimodal Perioperative Pain Management and Multimodal Strategies to Enhance Post Operative Outcomes. Post Operative Outcomes. http://www.phsa.ca/NR/rdonlyres/C879B328-3259-4753-BD39- http://www.phsa.ca/NR/rdonlyres/C879B328-3259-4753-BD39- 3E2C22408FCA/15620/9MultimodalPerioperativePainDrHamedUmedaly1.pdf. Accessed 3E2C22408FCA/15620/9MultimodalPerioperativePainDrHamedUmedaly1.pdf. Accessed 10-16-2008.10-16-2008.

Post-operative Pain ManagementCurrent PracticePost-operative Pain ManagementCurrent Practice

Multidisciplinary pain management team:Multidisciplinary pain management team:– SurgeonSurgeon

– AnesthesiologistAnesthesiologist

– Pain nursePain nurse

– PharmacistPharmacist

– Physical therapist/occupational therapistPhysical therapist/occupational therapist

– Floor nurseFloor nurse

White, Kehlet, et al, Anesthesia & Analgesia 2007 104:1380-1396White, Kehlet, et al, Anesthesia & Analgesia 2007 104:1380-1396

New Clinical Guidelines for post-operative PainNew Clinical Guidelines for post-operative Pain

Need for new guidelinesNeed for new guidelines

– US Veteran’s Health Administration- no updates since 2001US Veteran’s Health Administration- no updates since 200111

– Growing evidence that the efficacy of analgesic agents differs Growing evidence that the efficacy of analgesic agents differs between surgical proceduresbetween surgical procedures22

– Current post-operative pain management is not optimal Current post-operative pain management is not optimal

prospect prospect –– Pro Procedure-cedure-SpecSpecific post-operative Pain Working Group is ific post-operative Pain Working Group is a collaboration of international anesthesiologists and surgeonsa collaboration of international anesthesiologists and surgeons

– New New prospectprospect guidelines include: guidelines include:

• Procedure-specific evidence from review of literatureProcedure-specific evidence from review of literature

• Transferable evidence from other surgical proceduresTransferable evidence from other surgical procedures

• Guidelines specific to each surgical procedureGuidelines specific to each surgical procedure

• Recommendations to support clinical decisionsRecommendations to support clinical decisions

• Web-based data, quick and easy to access Web-based data, quick and easy to access

1 1 www.oqp.med.va.gov/cpg/PAIN/PAIN_about.doc Accessed 10-16-08www.oqp.med.va.gov/cpg/PAIN/PAIN_about.doc Accessed 10-16-08 2 2 Gray, Kehlet, er al. Gray, Kehlet, er al. Br J AnaesthBr J Anaesth 2005; 94 (6): 710–14. 2005; 94 (6): 710–14. 3 3 prospectprospect web site: www.postoppain.org. Accessed 10-16-2008. web site: www.postoppain.org. Accessed 10-16-2008.

Looking Ahead in Post-operative Pain Management Looking Ahead in Post-operative Pain Management

Expansion of anesthesiologist’s roleExpansion of anesthesiologist’s role– Identify pre-operative risk factorsIdentify pre-operative risk factors– Develop multimodal non-opioid analgesic regimensDevelop multimodal non-opioid analgesic regimens– Outreach services to physical therapy/occupational therapyOutreach services to physical therapy/occupational therapy

Practice changes Practice changes – Pre-operative conditioning for patients – Pre-operative conditioning for patients –

• aerobic and resistance exercises 3-4 weeks prior to aerobic and resistance exercises 3-4 weeks prior to surgerysurgery

– Intensified nurse-based preoperative patient educationIntensified nurse-based preoperative patient education– Multi-disciplinary approaches before and after surgeryMulti-disciplinary approaches before and after surgery

White, Kehlet, et al, Anesthesia & Analgesia 2007 104:1380-1396White, Kehlet, et al, Anesthesia & Analgesia 2007 104:1380-1396

Post-operative Pain Control with Extended-Release Bupivacaine Formulation After Hernia Repair

Post-operative Pain Control with Extended-Release Bupivacaine Formulation After Hernia Repair

• Current results from a Phase IIb, multicenter, double-blind, Current results from a Phase IIb, multicenter, double-blind,

parallel-group, placebo controlled dose-finding trialparallel-group, placebo controlled dose-finding trial

• SSABERABER™™ delivery system consists of a sucrose acetate delivery system consists of a sucrose acetate isobutyrate (SAIB) solvent with which the drug is mixedisobutyrate (SAIB) solvent with which the drug is mixed

-- POSIDURPOSIDUR™™(S(SABERABER™™-Bupivacaine) 5.0 mL significantly -Bupivacaine) 5.0 mL significantly improved mean pain intensity AUC on movement compared improved mean pain intensity AUC on movement compared with placebo post-surgery for 48 and 72 hourswith placebo post-surgery for 48 and 72 hours

-- Patients treated with SABER-Bupivacaine 5.0 mL required Patients treated with SABER-Bupivacaine 5.0 mL required significantly less opioid rescue medications post-operatively significantly less opioid rescue medications post-operatively compared with placebocompared with placebo

-- OverOver the study period, SABER-Bupivacaine 5.0 mL prolonged the study period, SABER-Bupivacaine 5.0 mL prolonged the time to first opioid use compared with placebo.the time to first opioid use compared with placebo.

Nicholson, Brown, et al American Hernia Society, 2008 Nicholson, Brown, et al American Hernia Society, 2008 AbstractAbstract

Extended-Release Liposomal Formulation of Bupivacaine for Post-Operative Pain Management after Hernia Repair Surgery

Extended-Release Liposomal Formulation of Bupivacaine for Post-Operative Pain Management after Hernia Repair Surgery

Materials and MethodsMaterials and Methods

This is a Phase 2, double-blind study, in which 41 patients were randomized This is a Phase 2, double-blind study, in which 41 patients were randomized within sequential cohorts to receive either DepoBupivacaine (175 mg in within sequential cohorts to receive either DepoBupivacaine (175 mg in Cohort 1, 225 mg in Cohort 2) or bupivacaine 100 mgCohort 1, 225 mg in Cohort 2) or bupivacaine 100 mg

The study drug was administered via surgical wound infiltration, in a 40-mL The study drug was administered via surgical wound infiltration, in a 40-mL total injection volumetotal injection volume

Supplemental use of analgesics – administered as needed after surgery – Supplemental use of analgesics – administered as needed after surgery – and pain scores – measured on a 0-100 mm visual analog scale (VAS) – and pain scores – measured on a 0-100 mm visual analog scale (VAS) – were recorded for 96 hours post-dosewere recorded for 96 hours post-dose

Wound healing scores (0-100 mm VAS) and adverse events (AE) were used Wound healing scores (0-100 mm VAS) and adverse events (AE) were used to monitor drug safetyto monitor drug safety

The study has a dose-escalation design and is currently ongoingThe study has a dose-escalation design and is currently ongoing– Preliminary data from the first two cohorts are reportedPreliminary data from the first two cohorts are reported

Presented: ASRA 31Presented: ASRA 31stst Annual Regional Anesthesia Meeting & Workshops, Rancho Mirage, California April 7, 2006. Annual Regional Anesthesia Meeting & Workshops, Rancho Mirage, California April 7, 2006.

Results - SafetyResults - Safety

There were no deaths in the study and no patients were There were no deaths in the study and no patients were discontinued because of adverse eventsdiscontinued because of adverse events

The incidence of local and systemic AEs was comparable across The incidence of local and systemic AEs was comparable across treatment groups and did not appear treatment- or dose-relatedtreatment groups and did not appear treatment- or dose-related– There was only one serious adverse event (SAE) in the study reported in the There was only one serious adverse event (SAE) in the study reported in the

DepoBupivacaine 225-mg group, which was noted as "Post-Operative DepoBupivacaine 225-mg group, which was noted as "Post-Operative Hematoma" and required overnight hospitalization for observationHematoma" and required overnight hospitalization for observation

– This SAE was considered ‘not related’ to the study drug and resolved in two This SAE was considered ‘not related’ to the study drug and resolved in two days without other intervention.days without other intervention.

Mean wound healing scores were 86.5 (SD=15.8), 89.4 Mean wound healing scores were 86.5 (SD=15.8), 89.4 (SD=11.9), and 79.8 (SD=14.27) in the DepoBupivacaine 175-mg, (SD=11.9), and 79.8 (SD=14.27) in the DepoBupivacaine 175-mg, DepoBupivacaine 225-mg, and bupivacaine 100-mg groups, DepoBupivacaine 225-mg, and bupivacaine 100-mg groups, respectively (where 0=worst healing and 100=best healing)respectively (where 0=worst healing and 100=best healing)

Presented: ASRA 31Presented: ASRA 31stst Annual Regional Anesthesia Meeting & Workshops, Rancho Mirage, California April 7, 2006. Annual Regional Anesthesia Meeting & Workshops, Rancho Mirage, California April 7, 2006.

Results - EfficacyResults - Efficacy

The proportion of patients requiring supplemental opioid The proportion of patients requiring supplemental opioid medication for POP management was higher in the bupivacaine medication for POP management was higher in the bupivacaine group (59%) compared with any of the DepoBupivacaine groups group (59%) compared with any of the DepoBupivacaine groups (25%)(25%)

Pain intensity scores at rest (VAS-R) and particularly with activity Pain intensity scores at rest (VAS-R) and particularly with activity (VAS-A) were lower for the DepoBupivacaine groups(VAS-A) were lower for the DepoBupivacaine groups– To assess pain intensity with activity, patients were asked to take a deep To assess pain intensity with activity, patients were asked to take a deep

breath and cough forcefullybreath and cough forcefully

– Differences in VAS-A scores were statistically significant (95% confidence Differences in VAS-A scores were statistically significant (95% confidence intervals) at 4, 8, 12, and 24 hours for DepoBupivacaine 175-mg dose and at intervals) at 4, 8, 12, and 24 hours for DepoBupivacaine 175-mg dose and at 8, 12, and 24 hours for DepoBupivacaine 225-mg dose, compared to the 8, 12, and 24 hours for DepoBupivacaine 225-mg dose, compared to the bupivacaine groupbupivacaine group

– There were no clear differences between study groups regarding the time There were no clear differences between study groups regarding the time from the end of surgery to the first administration of supplemental pain from the end of surgery to the first administration of supplemental pain medicationmedication

Presented: ASRA 31Presented: ASRA 31stst Annual Regional Anesthesia Meeting & Workshops, Rancho Mirage, California April 7, 2006. Annual Regional Anesthesia Meeting & Workshops, Rancho Mirage, California April 7, 2006.

Pain Intensity with Activity (VAS-A)Pain Intensity with Activity (VAS-A)

0

20

40

60

80

100

4 8 12 24 48 72 96

bupivacaine 100 mg

DepoBupivacaine 175 mg

DepoBupivacaine 225 mg

VA

S-A

(0

- 10

0 m

m)

VA

S-A

(0

- 10

0 m

m)

Time (hr)Time (hr)

Presented: ASRA 31Presented: ASRA 31stst Annual Regional Anesthesia Meeting & Workshops, Rancho Mirage, California April 7, 2006. Annual Regional Anesthesia Meeting & Workshops, Rancho Mirage, California April 7, 2006.