Update on associated factors and possible preventive strategies for chronic pain after surgery. As prevented at AAGBI January 2015.

1. Colin J.L. McCartneyColin J.L. McCartney
MBChB PhD FCARCSI FRCA FRCPCMBChB PhD FCARCSI FRCA FRCPC
Professor and Chair of AnaesthesiaProfessor and Chair of Anaesthesia
University of OttawaUniversity of Ottawa
Head of AnaesthesiaHead of Anaesthesia
The Ottawa HospitalThe Ottawa Hospital
Scientist,Scientist,
Ottawa Hospital Research InstituteOttawa Hospital Research Institute
Chronic Pain after Surgery:Chronic Pain after Surgery:
Does it exist and can weDoes it exist and can we
prevent it?prevent it?

2. Objectives (25 mins)Objectives (25 mins)
 Understand incidence of CPSP (5 mins)Understand incidence of CPSP (5 mins)
 Who are the populations at risk? (5 mins)Who are the populations at risk? (5 mins)
 What new approaches exist for preventingWhat new approaches exist for preventing
CPSP? (10 mins)CPSP? (10 mins)
 What does the future hold? (5 mins)What does the future hold? (5 mins)

3. SummarySummary
 CPSP common and varies by type of surgeryCPSP common and varies by type of surgery
 Preoperative pain and psychological factorsPreoperative pain and psychological factors
major predictorsmajor predictors
 Prevention possible with high qualityPrevention possible with high quality
perioperative pain relief including LA techniquesperioperative pain relief including LA techniques
and NMDA antagonists and surgical approachand NMDA antagonists and surgical approach
 Future management possibilities include novelFuture management possibilities include novel
therapeutic, psychological andtherapeutic, psychological and
pharmacogenomic approachespharmacogenomic approaches

4. Incidence ofIncidence of
Chronic Post-Surgical PainChronic Post-Surgical Pain
 Pain after surgery of primary concern toPain after surgery of primary concern to
patients (Apfelbaum et al 1999)patients (Apfelbaum et al 1999)
 Acute postoperative pain remainsAcute postoperative pain remains
undertreatedundertreated
 Incidence of severe acute pain a problemIncidence of severe acute pain a problem
 Severe acute pain associated with CPSPSevere acute pain associated with CPSP
 Definition: pain >2 months after surgeryDefinition: pain >2 months after surgery

6. A&A 2003

7.  300 patients300 patients
 2/3 had moderate-severe pain after2/3 had moderate-severe pain after
surgerysurgery
 No change from 10 years earlierNo change from 10 years earlier
Gan TJ et al CMRO 2014

8. Or does it?

10.  5130 patients attending chronic pain5130 patients attending chronic pain
clinicsclinics
 Surgery contributed to pain in 22.5%Surgery contributed to pain in 22.5%
 Research needed into: aetiology andResearch needed into: aetiology and
procedures contributing to highest risk ofprocedures contributing to highest risk of
CPSP.CPSP.
 Preventive strategiesPreventive strategies
Pain 1998

11.  Prevalence of persistent postsurgical painPrevalence of persistent postsurgical pain
 12982 participants/3111 undergone surgery12982 participants/3111 undergone surgery
within 3 yearswithin 3 years
 Persistent pain in 40.4%. Mod-Severe 18.3%Persistent pain in 40.4%. Mod-Severe 18.3%

13. Poulakka PA et al EJA 2010

14. Differentiating CPSPDifferentiating CPSP

15.  Systematic review. 281 studies assessedSystematic review. 281 studies assessed
investigating PSPS in 11 surgical typesinvestigating PSPS in 11 surgical types
 Prevalence of NeuP determined using NeuPPrevalence of NeuP determined using NeuP
grading systemgrading system
 Prevalence of NeuP high after thoracic andPrevalence of NeuP high after thoracic and
breast surgery (66/68%). 31% after groin herniabreast surgery (66/68%). 31% after groin hernia
repair and 6% after THA and TKArepair and 6% after THA and TKA
 Prevalence of PneuP varies by type of surgeryPrevalence of PneuP varies by type of surgery
and probability of nerve injuryand probability of nerve injury

16. Risk Factors for CPSP?Risk Factors for CPSP?
 Preoperative: Pain, Repeat surgery,Preoperative: Pain, Repeat surgery,
Psychological factors, Female gender andPsychological factors, Female gender and
younger age, Genetic predispositionyounger age, Genetic predisposition
 Intraoperative: Surgical approach andIntraoperative: Surgical approach and
risks of nerve injuryrisks of nerve injury
 Postoperative: Acute Pain, Radiation Rx,Postoperative: Acute Pain, Radiation Rx,
Neurotoxic chemotherapy, Anxiety andNeurotoxic chemotherapy, Anxiety and
Depression, NeuroticismDepression, Neuroticism
McIntyre et al 2010

17. What can we do about theWhat can we do about the
problem?problem?
 Regional anaesthesia techniquesRegional anaesthesia techniques
 Systemic drug interventionsSystemic drug interventions
 Modified surgical techniquesModified surgical techniques
 Focus on postoperative pain controlFocus on postoperative pain control

18. Regional anesthesia techniquesRegional anesthesia techniques

19.  23 RCTs in total23 RCTs in total
 Pooled 3 studies for epidural afterPooled 3 studies for epidural after
thoracotomy and 2 for PVB after breastthoracotomy and 2 for PVB after breast
surgerysurgery
 Unable to pool data from other studies dueUnable to pool data from other studies due
to marked heterogeneityto marked heterogeneity

20. Andreae MH et al BJA 2013

21. Perioperative pharmacotherapyPerioperative pharmacotherapy
 KetamineKetamine
 LidocaineLidocaine
 GabapentinoidsGabapentinoids
 NSAIDSNSAIDS

22. KetamineKetamine

23. 2013 Cochrane Collaboration

25.  No long term benefit for:No long term benefit for:
– GabapentinGabapentin
– PregabalinPregabalin
– NSAIDSNSAIDS
– CorticosteroidsCorticosteroids
– MexilitineMexilitine
2013 Cochrane Collaboration

26. Modified Surgical TechniquesModified Surgical Techniques

29. Future PossibilitiesFuture Possibilities
 Impact of psychological factorsImpact of psychological factors
 Pharmacogenomics and personalizedPharmacogenomics and personalized
medicinemedicine
 Novel ‘analgesic’ agentsNovel ‘analgesic’ agents

30. Psychological FactorsPsychological Factors

31.  Preoperative painPreoperative pain
 Pain catastrophizingPain catastrophizing
 Mental healthMental health
 Pain at other sitesPain at other sites

32. Pain 2013

33. Predictive Factors Post-Predictive Factors Post-
MastectomyMastectomy
Schreiber et al Pain 2013

35. Pain GeneticsPain Genetics

36. PharmacogenomicsPharmacogenomics

37. Genetics of PainGenetics of Pain
 3 variants (haplotypes) of gene encoding3 variants (haplotypes) of gene encoding
COMT predicting low, moderate and highCOMT predicting low, moderate and high
sensitivity to painsensitivity to pain
 Encompass 96% of humansEncompass 96% of humans
 Low COMT levels predict high painLow COMT levels predict high pain
sensitivity and risk of developing TMDsensitivity and risk of developing TMD
 Inhibition of COMT in rat model increasesInhibition of COMT in rat model increases
pain sensitivitypain sensitivity
Diatchenko L et al 2005

38.  CPSP is likely 50% influenced by geneticCPSP is likely 50% influenced by genetic
determinantsdeterminants
 Identifying genetic basis of CPSP couldIdentifying genetic basis of CPSP could
lead to significant improvement inlead to significant improvement in
treatmenttreatment
 Prediction of CPSP, PharmacogenomicsPrediction of CPSP, Pharmacogenomics
 Improved treatmentsImproved treatments
CJA: published ahead of print

39. Novel neuroactive agentsNovel neuroactive agents
 Not analgesic per seNot analgesic per se
 Prevent mechanism of transition to chronicPrevent mechanism of transition to chronic
painpain
 rhBDNF, neuroprotective agents (e.g.rhBDNF, neuroprotective agents (e.g.
acetyl l-carnitine) and anti-oxidantsacetyl l-carnitine) and anti-oxidants
 Early promising resultsEarly promising results
Bordet T et al Neurotherapeutics 2009

40. SummarySummary
 CPSP common and varies by type of surgeryCPSP common and varies by type of surgery
 Preoperative pain and psychological factorsPreoperative pain and psychological factors
major predictorsmajor predictors
 Prevention possible with high qualityPrevention possible with high quality
perioperative pain relief including LA techniquesperioperative pain relief including LA techniques
and NMDA antagonists and surgical approachand NMDA antagonists and surgical approach
 Future management possibilities include novelFuture management possibilities include novel
therapeutic, psychological andtherapeutic, psychological and
pharmacogenomic approachespharmacogenomic approaches

41. Good Acute Pain Control MajorGood Acute Pain Control Major
Concern for PatientsConcern for Patients
Apfelbaum et al A&A 2003

42. Acute pain controlAcute pain control
 Use regional anaesthesia where possibleUse regional anaesthesia where possible
 Use NSAIDS, paracetamol in multimodalUse NSAIDS, paracetamol in multimodal
regimenregimen
 For higher risk cases use ketamine and/orFor higher risk cases use ketamine and/or
lidocaine infusion during surgerylidocaine infusion during surgery
 Gabapentin/Pregabalin useful for acuteGabapentin/Pregabalin useful for acute
pain control and reduction of opioidpain control and reduction of opioid
consumptionconsumption