Redefining Local Anesthetic

1
Redefining Local Anesthetic Infiltration Therapy
Dr. Eugene Viscusi Department of
Anesthesiology Jefferson Medical College
2
Post-operative Pain ManagementTraditional
Methods

• Previous guidelines for post-operative analgesics
  were one size fits all -- general
  recommendations for all surgical procedures based
  on pooled data1
• Anesthesiologists primary role in traditional
  setting2
• Pre-operative preparation
• Provide optimal surgical conditions
• Minimize pain immediately after surgery

1 Kehlet, Anesthesiology Clin N Am 2005
23203-210 2 White, Kehlet, et al, Anesthesia
Analgesia 2007 1041380-1396
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 Veterans Health Administration5

1 Porter, Davis, An Royal Coll Surgeons Eng 1985
67 293-294. 2 Werner, Soholm, et al Anesth Analg
2002 951361-72. 3 Dahl, Rosenberg, et al, Br J
Anes 1990 64581-520. 4 Kehlet, Bri J Anes
199778606-617. 5 www.oqp.med.va.gov/cpg/PAIN/PAI
N_about.doc Accessed 10-116-08
4
Suboptimal Management of Post-operative Pain
Patients 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.
1995831090-1904. Apfelbaum JL, Chen C, Mehta
SS, Gan TJ. Anesth Analg. 200397534-540.
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
2007 1041380-1396 2 European Society of Regional
Anaesthesia and Pain Therapy, post-operative Pain
ManagementGood Clinical Practice. 3 Umedaly,
Multimodal Perioperative Pain Management and
Multimodal Strategies to Enhance Post Operative
Outcomes. http//www.phsa.ca/NR/rdonlyres/C879B32
8-3259-4753-BD39- 3E2C22408FCA/15620/9Multimodal
PerioperativePainDrHamedUmedaly1.pdf. Accessed
10-16-2008
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
78614
7
Multimodal Management of Post-operative Pain

• Post-operative issues
• Pain management
• Nausea and Vomiting
• Ileus and constipation
• PT

• 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

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Benefits of Multimodal Pain Management

• Benefits
• 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 199778606-617. 2 Umedaly,
Multimodal Perioperative Pain Management and
Multimodal Strategies to Enhance Post Operative
Outcomes. http//www.phsa.ca/NR/rdonlyres/C879B32
8-3259-4753-BD39- 3E2C22408FCA/15620/9Multimodal
PerioperativePainDrHamedUmedaly1.pdf. Accessed
10-16-2008.
9
Post-operative Pain ManagementCurrent Practice

• Multidisciplinary pain management team
• Surgeon
• Anesthesiologist
• Pain nurse
• Pharmacist
• Physical therapist/occupational therapist
• Floor nurse

White, Kehlet, et al, Anesthesia Analgesia
2007 1041380-1396
10
New Clinical Guidelines for post-operative Pain

• Need for new guidelines
• US Veterans 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 www.oqp.med.va.gov/cpg/PAIN/PAIN_about.doc
Accessed 10-16-08 2 Gray, Kehlet, er al. Br J
Anaesth 2005 94 (6) 71014. 3 prospect web
site www.postoppain.org. Accessed 10-16-2008.
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Looking Ahead in Post-operative Pain Management

• Expansion of anesthesiologists 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 2007
1041380-1396
12
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 0-100 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.
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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 (SD15.8),
  89.4 (SD11.9), and 79.8 (SD14.27) in the
  DepoBupivacaine 175-mg, DepoBupivacaine 225-mg,
  and bupivacaine 100-mg groups, respectively
  (where 0worst healing and 100best healing)

Presented ASRA 31st Annual Regional Anesthesia
Meeting Workshops, Rancho Mirage, California
April 7, 2006.
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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 (0 - 100 mm)
40
20
0
4
8
12
24
48
72
96
Time (hr)
Presented ASRA 31st Annual Regional Anesthesia
Meeting Workshops, Rancho Mirage, California
April 7, 2006.