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To Block or Not to Block:
Prevention of Persistent
Postoperative Pain
Edward R. Mariano, M.D., M.A.S.
Professor of Anesthesiology, Perioperative & Pain Medicine
Stanford University School of Medicine
Chief, Anesthesiology and Perioperative Care
Veterans Affairs Palo Alto Health Care System
@EMARIANOMD
Persistent Postsurgical Pain
Financial Disclosures
 Halyard Health, B Braun – Unrestricted
educational program funding paid to my
institution
The contents of the following presentation
are solely the responsibility of the speaker
without input from any of the above
companies.
Persistent Postsurgical Pain
Chronic Pain after Surgery
Persistent Postsurgical Pain
Kehlet H, et al. Lancet 2006;367:1618
Persistent Postsurgical Pain
Overview
 Risk Factors for Persistent Postsurgical
Pain (PPSP)
 Potential Role of Regional Anesthesia and
Analgesia
 Pharmacologic Interventions for PPSP
Persistent Postsurgical Pain
Overview
 Risk Factors for Persistent Postsurgical
Pain (PPSP)
 Potential Role of Regional Anesthesia and
Analgesia
 Pharmacologic Interventions for PPSP
Persistent Postsurgical Pain
Risk Factors for PPSP
 Patient phenotypic factors
– Preexisting pain before surgery
– High consumption of analgesic medications
preoperatively
– Catastrophizing
– Severe acute postoperative pain
 Patient genetic factors (~45%)
 Nerve injury during surgery, inflammation,
and neuronal plasticity
Richebe P, et al. CJA 2015;62:1329
Clarke H, et al. CJA 2015;62:294
Persistent Postsurgical Pain
Bayman EO, et al. Anesth 2017 epub
Persistent Postsurgical Pain
Catastrophizing as a Risk Factor
157 Knee
Replacement
Patients
Pain
Catastrophizing
Scale
≥16 considered
high score
Riddle DL, et al. CORR 2010;468:798
Persistent Postsurgical Pain
Catastrophizing as a Risk Factor
Riddle DL, et al. CORR 2010;468:798
Persistent Postsurgical Pain
Opioid-Induced Hyperalgesia
Angst MS, et al. Pain 2003;106:49
Persistent Postsurgical Pain
Overview
 Risk Factors for Persistent Postsurgical
Pain (PPSP)
 Potential Role of Regional Anesthesia and
Analgesia
 Pharmacologic Interventions for PPSP
Persistent Postsurgical Pain
Kehlet H, et al. Lancet 2006;367:1618
How Can Regional
Anesthesia Help?
Persistent Postsurgical Pain
What Regional Anesthesia Does
 Mitigates maximal pain intensity after
surgery1
 Decreases opioid consumption2 (maybe
less opioid-induced hyperalgesia)
 Facilitates early mobility3
 Avoids immobility which can produce
hyperalgesia and persistent pain4,5
1. Ilfeld BM. A&A 2011;113(4):904
2. Richman JM, et al. A&A 2006;102:248
3. Ilfeld & Mariano, et al. Pain 2010;150:477
4. Ohmichi Y, et al. Eur J Pain 2012;16:338
5. Guo TZ, et al. J Pain 2014;15:1033
Persistent Postsurgical Pain
Preventing PPSP
 Primary prevention: avoid injury/surgery
 Secondary prevention: early intervention
to prevent transition from acute to chronic
Gilron & Kehlet. CJA 2014;61:101
Persistent Postsurgical Pain
Chronic Pain after Thoracotomy
 Incidence is approximately 50%
– 3-16% report pain as moderate-severe
 Heterogeneity in study designs
 Many contributing factors: patients,
surgical technique, pre- and postop pain
 To date, no convincing evidence that PVB
decreases chronic pain after thoracotomy
Wildgaard & Kehlet. Eur J CTS 2009;36:170
Persistent Postsurgical Pain
Chronic Pain after Breast Surgery
 Survey of 479 women who underwent
breast surgery over a 4-year period
 59% response rate
 Prevalence of pain after >1 year postop:
– Mastectomy/reconstruction = 49%
– Mastectomy alone = 31%
– Augmentation = 38%
– Reduction = 22%
Wallace MS, et al. Pain 1996;66:195
Persistent Postsurgical Pain
Chronic Pain after Breast Surgery
 Secondary outcome of previously-published RCT
– Immediate postop pain less in PVB group (p<0.01)
 Less pain in PVB group at 6 (p=0.029; n=60) and
12 mos (p=0.003; n=59)
Kairaluoma P, et al. A&A 2004;99:1837
Persistent Postsurgical Pain
Chronic Pain after Breast Surgery
 Meta-analysis: 3 studies assessed this
outcome (n=167)
 All PVB-GA vs. GA
 At 6 mos, RR=0.16, 95%CI (0.02-1.13)
– No difference (crosses 1)
 At 12 mos, RR=0.61, 95%CI (0.08-4.90)
– No difference (crosses 1)
Schnabel A, et al. BJA 2010;105:842
Persistent Postsurgical Pain
 3 day infusion of ropivacaine vs. saline
 At 12 months:
– 13% pain-induced dysfunction for ropivacaine
vs. 47% for saline (p=0.011)
– Mean BPI 1.6 ± 4.6 for ropivacaine vs. 5.9 ±
11.3 for saline (p=0.007)
Ilfeld BM, et al. Ann Surg Onc 2015;22:2017
Persistent Postsurgical Pain
Is the Infusion Long Enough?
Lavand’homme, et al. CORR 2014;472:1409
TKA
Patients
Normal
Persistent Pain
Neuropathic Pain
Persistent Postsurgical Pain
Overview
 Risk Factors for Persistent Postsurgical
Pain (PPSP)
 Potential Role of Regional Anesthesia and
Analgesia
 Pharmacologic Interventions for PPSP
Persistent Postsurgical Pain
Think Multimodal
Anesthesiology 2012;116:248
Persistent Postsurgical Pain
Ketamine
Persistent Postsurgical Pain
Where Ketamine Works
Himmelseher & Durieux. Anesth 2005;102:211
Persistent Postsurgical Pain
When to Administer Ketamine
Himmelseher & Durieux. Anesth 2005;102:211
Persistent Postsurgical Pain
Ketamine and OIH
Angst MS, et al. Pain 2003;106:49
Persistent Postsurgical Pain
Pregabalin
1. Lavand’homme, et al. CORR 2014;472:1409
2. Buvanendran A, et al. A&A 2010;110:199
 For TKA, incidence of PPSP may be as
high as 58% with 11% reporting
neuropathic symptoms1
 Pregabalin may decrease neuropathic
PPSP after TKA2
– 0% vs. 9% (placebo) at 3 months (p=0.001)
– 0% vs. 5% (placebo) at 6 months (p=0.014)
Persistent Postsurgical Pain
Gabapentin
Clarke H, et al. A&A 2012;115:428
Persistent Postsurgical Pain
Framework for Approaching PPSP
Gilron & Kehlet. CJA 2014;61:101
Persistent Postsurgical Pain
Overview
 We discussed:
– Risk Factors for Persistent Postsurgical
Pain (PPSP)
– Potential Role of Regional Anesthesia
and Analgesia
– Pharmacologic Interventions for PPSP

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Regional Anesthesia in the Prevention of Persistent Postsurgical Pain

  • 1. To Block or Not to Block: Prevention of Persistent Postoperative Pain Edward R. Mariano, M.D., M.A.S. Professor of Anesthesiology, Perioperative & Pain Medicine Stanford University School of Medicine Chief, Anesthesiology and Perioperative Care Veterans Affairs Palo Alto Health Care System @EMARIANOMD
  • 2. Persistent Postsurgical Pain Financial Disclosures  Halyard Health, B Braun – Unrestricted educational program funding paid to my institution The contents of the following presentation are solely the responsibility of the speaker without input from any of the above companies.
  • 4. Persistent Postsurgical Pain Kehlet H, et al. Lancet 2006;367:1618
  • 5. Persistent Postsurgical Pain Overview  Risk Factors for Persistent Postsurgical Pain (PPSP)  Potential Role of Regional Anesthesia and Analgesia  Pharmacologic Interventions for PPSP
  • 6. Persistent Postsurgical Pain Overview  Risk Factors for Persistent Postsurgical Pain (PPSP)  Potential Role of Regional Anesthesia and Analgesia  Pharmacologic Interventions for PPSP
  • 7. Persistent Postsurgical Pain Risk Factors for PPSP  Patient phenotypic factors – Preexisting pain before surgery – High consumption of analgesic medications preoperatively – Catastrophizing – Severe acute postoperative pain  Patient genetic factors (~45%)  Nerve injury during surgery, inflammation, and neuronal plasticity Richebe P, et al. CJA 2015;62:1329 Clarke H, et al. CJA 2015;62:294
  • 8. Persistent Postsurgical Pain Bayman EO, et al. Anesth 2017 epub
  • 9. Persistent Postsurgical Pain Catastrophizing as a Risk Factor 157 Knee Replacement Patients Pain Catastrophizing Scale ≥16 considered high score Riddle DL, et al. CORR 2010;468:798
  • 10. Persistent Postsurgical Pain Catastrophizing as a Risk Factor Riddle DL, et al. CORR 2010;468:798
  • 11. Persistent Postsurgical Pain Opioid-Induced Hyperalgesia Angst MS, et al. Pain 2003;106:49
  • 12. Persistent Postsurgical Pain Overview  Risk Factors for Persistent Postsurgical Pain (PPSP)  Potential Role of Regional Anesthesia and Analgesia  Pharmacologic Interventions for PPSP
  • 13. Persistent Postsurgical Pain Kehlet H, et al. Lancet 2006;367:1618 How Can Regional Anesthesia Help?
  • 14. Persistent Postsurgical Pain What Regional Anesthesia Does  Mitigates maximal pain intensity after surgery1  Decreases opioid consumption2 (maybe less opioid-induced hyperalgesia)  Facilitates early mobility3  Avoids immobility which can produce hyperalgesia and persistent pain4,5 1. Ilfeld BM. A&A 2011;113(4):904 2. Richman JM, et al. A&A 2006;102:248 3. Ilfeld & Mariano, et al. Pain 2010;150:477 4. Ohmichi Y, et al. Eur J Pain 2012;16:338 5. Guo TZ, et al. J Pain 2014;15:1033
  • 15. Persistent Postsurgical Pain Preventing PPSP  Primary prevention: avoid injury/surgery  Secondary prevention: early intervention to prevent transition from acute to chronic Gilron & Kehlet. CJA 2014;61:101
  • 16. Persistent Postsurgical Pain Chronic Pain after Thoracotomy  Incidence is approximately 50% – 3-16% report pain as moderate-severe  Heterogeneity in study designs  Many contributing factors: patients, surgical technique, pre- and postop pain  To date, no convincing evidence that PVB decreases chronic pain after thoracotomy Wildgaard & Kehlet. Eur J CTS 2009;36:170
  • 17. Persistent Postsurgical Pain Chronic Pain after Breast Surgery  Survey of 479 women who underwent breast surgery over a 4-year period  59% response rate  Prevalence of pain after >1 year postop: – Mastectomy/reconstruction = 49% – Mastectomy alone = 31% – Augmentation = 38% – Reduction = 22% Wallace MS, et al. Pain 1996;66:195
  • 18. Persistent Postsurgical Pain Chronic Pain after Breast Surgery  Secondary outcome of previously-published RCT – Immediate postop pain less in PVB group (p<0.01)  Less pain in PVB group at 6 (p=0.029; n=60) and 12 mos (p=0.003; n=59) Kairaluoma P, et al. A&A 2004;99:1837
  • 19. Persistent Postsurgical Pain Chronic Pain after Breast Surgery  Meta-analysis: 3 studies assessed this outcome (n=167)  All PVB-GA vs. GA  At 6 mos, RR=0.16, 95%CI (0.02-1.13) – No difference (crosses 1)  At 12 mos, RR=0.61, 95%CI (0.08-4.90) – No difference (crosses 1) Schnabel A, et al. BJA 2010;105:842
  • 20. Persistent Postsurgical Pain  3 day infusion of ropivacaine vs. saline  At 12 months: – 13% pain-induced dysfunction for ropivacaine vs. 47% for saline (p=0.011) – Mean BPI 1.6 ± 4.6 for ropivacaine vs. 5.9 ± 11.3 for saline (p=0.007) Ilfeld BM, et al. Ann Surg Onc 2015;22:2017
  • 21. Persistent Postsurgical Pain Is the Infusion Long Enough? Lavand’homme, et al. CORR 2014;472:1409 TKA Patients Normal Persistent Pain Neuropathic Pain
  • 22. Persistent Postsurgical Pain Overview  Risk Factors for Persistent Postsurgical Pain (PPSP)  Potential Role of Regional Anesthesia and Analgesia  Pharmacologic Interventions for PPSP
  • 23. Persistent Postsurgical Pain Think Multimodal Anesthesiology 2012;116:248
  • 25. Persistent Postsurgical Pain Where Ketamine Works Himmelseher & Durieux. Anesth 2005;102:211
  • 26. Persistent Postsurgical Pain When to Administer Ketamine Himmelseher & Durieux. Anesth 2005;102:211
  • 27. Persistent Postsurgical Pain Ketamine and OIH Angst MS, et al. Pain 2003;106:49
  • 28. Persistent Postsurgical Pain Pregabalin 1. Lavand’homme, et al. CORR 2014;472:1409 2. Buvanendran A, et al. A&A 2010;110:199  For TKA, incidence of PPSP may be as high as 58% with 11% reporting neuropathic symptoms1  Pregabalin may decrease neuropathic PPSP after TKA2 – 0% vs. 9% (placebo) at 3 months (p=0.001) – 0% vs. 5% (placebo) at 6 months (p=0.014)
  • 30. Persistent Postsurgical Pain Framework for Approaching PPSP Gilron & Kehlet. CJA 2014;61:101
  • 31. Persistent Postsurgical Pain Overview  We discussed: – Risk Factors for Persistent Postsurgical Pain (PPSP) – Potential Role of Regional Anesthesia and Analgesia – Pharmacologic Interventions for PPSP