1. Redefining Local Anesthetic
Infiltration Therapy
Dr. Eugene Viscusi
Department of Anesthesiology
Jefferson Medical College

2. Post-operative Pain Management: Traditional Methods
Previous guidelines for post-operative analgesics were “one size fits all” -- general recommendations for all surgical procedures based on pooled data1
Anesthesiologist’s primary role in traditional setting2
Pre-operative preparation
Provide optimal surgical conditions
Minimize pain immediately after surgery
1 Kehlet, Anesthesiology Clin N Am :
2 White, Kehlet, et al, Anesthesia & Analgesia :

3. Early Changes in Post-operative Pain Management
Early changes in therapy included:
1985 – Injection of bupivacaine following wound closure: patient free of pain for 11.5 hours1
1985 – First acute pain services established in the US and Germany2
1990 – “Balanced” analgesia used to prevent post-operative pain in colorectal surgery3
1997 – Kehlet introduces multimodal concept for post-operative care4
Early clinical guidelines for post-operative pain
2001 – US Veteran’s Health Administration5
1 Porter, Davis, An Royal Coll Surgeons Eng 1985; 67:
2 Werner, Soholm, et al Anesth Analg 2002; 95:
3 Dahl, Rosenberg, et al, Br J Anes 1990; 64:
4 Kehlet, Bri J Anes 1997;78:
5 Accessed

4. Suboptimal Management of Post-operative Pain
Patient’s worst pain
“Pain can be relieved effectively in 90% of patients, but is not relieved effectively in 80% of patients.”
Warfield CA, Kahn CH. Anesthesiology. 1995;83: Apfelbaum JL, Chen C, Mehta SS, Gan TJ. Anesth Analg. 2003;97:

5. Multimodal Management of Post-operative Pain
Definition: Multimodal (balanced) anesthesia involves use of two or more analgesic agents with different mechanisms of action to achieve optimal analgesic effect by additive or synergistic effects.1,2
“Pain neurobiology is a complex of dynamic interrelated systems. Unimodal analgesia cannot be sufficient to provide optimal pain management. Additive and synergistic effects of multiple modes should improve outcomes.” Hamed Umedaly, MD3
1 White, Kehlet, et al, Anesthesia & Analgesia :
2 European Society of Regional Anaesthesia and Pain Therapy, post-operative Pain Management—Good Clinical Practice.
3 Umedaly, Multimodal Perioperative Pain Management and Multimodal Strategies to Enhance
Post Operative Outcomes.
3E2C22408FCA/15620/9MultimodalPerioperativePainDrHamedUmedaly1.pdf. Accessed

6. Multimodal and Multi-Disciplinary Approach
Controlling post-operative physiology
Pre-operative
information Attenuation Pain Exercise Enteral Growth
and teaching of stress relief nutrition factors
Reduced morbidity and accelerated convalescence
Adapted from graph: Kehlet, Bri J of Anes 1997; 78:614

7. Multimodal Management of Post-operative Pain
Pre-operative issues
Risk stratification
Anesthetic and analgesic plan
Intra-operative issues
Local anesthesia
Infiltration
Regional anesthesia
IV regional, peripheral nerve blocks, neuraxial blocks
General anesthesia
Post-operative issues
Pain management
Nausea and Vomiting
Ileus and constipation PT

8. Benefits of Multimodal Pain Management
Reduced morbidity
Enhanced post-operative recovery of organ functions
Accelerated convalescence1
Reduction of opioid use
Reduced doses of each analgesic
Improved antinociception due to synergistic/additive effects
Reduction in severity of side effects2
1 Kehlet, Bri J Anes 1997;78:
2 Umedaly, Multimodal Perioperative Pain Management and Multimodal Strategies to Enhance
Post Operative Outcomes.
3E2C22408FCA/15620/9MultimodalPerioperativePainDrHamedUmedaly1.pdf. Accessed

9. Post-operative Pain Management Current Practice
Multidisciplinary pain management team:
Surgeon
Anesthesiologist
Pain nurse
Pharmacist
Physical therapist/occupational therapist
Floor nurse
White, Kehlet, et al, Anesthesia & Analgesia :

10. New Clinical Guidelines for post-operative Pain
Need for new guidelines
US Veteran’s Health Administration- no updates since 20011
Growing evidence that the efficacy of analgesic agents differs between surgical procedures2
Current post-operative pain management is not optimal
prospect – Procedure-Specific post-operative Pain Working Group is a collaboration of international anesthesiologists and surgeons
New prospect guidelines include:
Procedure-specific evidence from review of literature
Transferable evidence from other surgical procedures
Guidelines specific to each surgical procedure
Recommendations to support clinical decisions
Web-based data, quick and easy to access
1 Accessed
2 Gray, Kehlet, er al. Br J Anaesth 2005; 94 (6): 710–14.
3 prospect web site: Accessed

11. Looking Ahead in Post-operative Pain Management
Expansion of anesthesiologist’s role
Identify pre-operative risk factors
Develop multimodal non-opioid analgesic regimens
Outreach services to physical therapy/occupational therapy
Practice changes
Pre-operative conditioning for patients –
aerobic and resistance exercises 3-4 weeks prior to surgery
Intensified nurse-based preoperative patient education
Multi-disciplinary approaches before and after surgery
White, Kehlet, et al, Anesthesia & Analgesia :

12. Nicholson, Brown, et al American Hernia Society, 2008 Abstract
Post-operative Pain Control with Extended-Release Bupivacaine Formulation After Hernia Repair
Current results from a Phase IIb, multicenter, double-blind, parallel-group, placebo controlled dose-finding trial
SABER™ delivery system consists of a sucrose acetate isobutyrate (SAIB) solvent with which the drug is mixed
- POSIDUR™(SABER™-Bupivacaine) 5.0 mL significantly improved mean pain intensity AUC on movement compared with placebo post-surgery for 48 and 72 hours
- Patients treated with SABER-Bupivacaine 5.0 mL required significantly less opioid rescue medications post-operatively compared with placebo
- Over the study period, SABER-Bupivacaine 5.0 mL prolonged the time to first opioid use compared with placebo.
Nicholson, Brown, et al American Hernia Society, 2008 Abstract

13. Extended-Release Liposomal Formulation of Bupivacaine for Post-Operative Pain Management after Hernia Repair Surgery
Materials and Methods
This is a Phase 2, double-blind study, in which 41 patients were randomized within sequential cohorts to receive either DepoBupivacaine (175 mg in Cohort 1, 225 mg in Cohort 2) or bupivacaine 100 mg
The study drug was administered via surgical wound infiltration, in a 40-mL total injection volume
Supplemental use of analgesics – administered as needed after surgery – and pain scores – measured on a mm visual analog scale (VAS) – were recorded for 96 hours post-dose
Wound healing scores (0-100 mm VAS) and adverse events (AE) were used to monitor drug safety
The study has a dose-escalation design and is currently ongoing
Preliminary data from the first two cohorts are reported
Presented: ASRA 31st Annual Regional Anesthesia Meeting & Workshops, Rancho Mirage, California April 7, 2006.

14. Results - Safety
There were no deaths in the study and no patients were discontinued because of adverse events
The incidence of local and systemic AEs was comparable across treatment groups and did not appear treatment- or dose-related
There was only one serious adverse event (SAE) in the study reported in the DepoBupivacaine 225-mg group, which was noted as "Post-Operative Hematoma" and required overnight hospitalization for observation
This SAE was considered ‘not related’ to the study drug and resolved in two days without other intervention.
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, DepoBupivacaine 225-mg, and bupivacaine 100-mg groups, respectively (where 0=worst healing and 100=best healing)
Presented: ASRA 31st Annual Regional Anesthesia Meeting & Workshops, Rancho Mirage, California April 7, 2006.

15. Results - Efficacy
The proportion of patients requiring supplemental opioid medication for POP management was higher in the bupivacaine group (59%) compared with any of the DepoBupivacaine groups (25%)
Pain intensity scores at rest (VAS-R) and particularly with activity (VAS-A) were lower for the DepoBupivacaine groups
To assess pain intensity with activity, patients were asked to take a deep breath and cough forcefully
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 8, 12, and 24 hours for DepoBupivacaine 225-mg dose, compared to the bupivacaine group
There were no clear differences between study groups regarding the time from the end of surgery to the first administration of supplemental pain medication
Presented: ASRA 31st Annual Regional Anesthesia Meeting & Workshops, Rancho Mirage, California April 7, 2006.

16. Pain Intensity with Activity (VAS-A)
100
bupivacaine 100 mg
DepoBupivacaine 175 mg
DepoBupivacaine 225 mg 80 60
VAS-A ( mm) 40 20 4 8 12 24 48 72 96
Time (hr)
Presented: ASRA 31st Annual Regional Anesthesia Meeting & Workshops, Rancho Mirage, California April 7, 2006.