Chronic pain after breast surgery Dr John E. Williams Consultant in Anaesthesia and Pain Management Royal Marsden Hospital
GOOD NEWS! Most patients heal normally after surgery & return to baseline functional status BAD NEWS! 1. Some operations & some patients...at risk of developing chronic pain +/- long term opioid use 2. Significant impact..physically & socially, economically $1m in a 30yr old (Labatt, 2000) 3. Predictive factors..but we are a long way from determining precise role. 4. Epidemic of CPSP (Katz,2017) 5. Complex area, aetiologically and clinically (Macrae, 1998, 2008)
Questions? Why is this an important topic? How big a problem is it? Why do some people develop the problem and not others? Clinical manifestations and impact? Why is Pain predictive of more Pain? Does the pain get better? What can we do as Anaesthetists / AHP s?...prevention and treatment What can we discuss with Surgeons?...Patients? What is the way forward?
Is this a real problem? & Why is it important? 1. COMMON Once thought to be rare recently reported incidence > 50%, under-recognised, misdiagnosed & neglected Survivor population increasing, huge impact for humanitarian, medical & economic reasons Causes additional disability & psychological distress Chemo- & radio-therapy additional causes of pain Spectre of recurrent disease 2. PREVENTION New focus on treatment & prevention Model of acute to chronic mechanisms Integration of pain services with other clinical groups
Case Vignette Mrs. MB, age 45 Mastectomy & axillary dissection, RT Presents with severe chronic pain Severe limitation of movement MRI excludes recurrent disease
Pain & disability Capsulitis Muscle spasm Pain
Cording
History Sherman et al, PAIN (1984) Chronic phantom pain in 5,000 American Veterans. 80% pain. 1% lasting effect of treatments Crombie et al, PAIN (1998) Cut and Thrust: antecedent surgery among patients attending a chronic pain clinic. Surgery caused pain in 23% Macrea, BJA (1998, 2008) Chronic postsurgical pain.
Incidence - operations Type of operation Incidence of chronic pain 1. Amputation 30-50% 15,000 2. Mastectomy 20-30% 18,000 3. Thoracotomy 30-60% Heart bypass surgery 30-50% 30,000 Caesarean section 6% 139,000 Cholecystectomy 5-50% 51,000 Hernia 5-35% 75,000 Laparotomy? 30,000 No. of ops (2006) Dental root canal surgery (PAIN, 2016) 10%?
Prevalence of chronic pain after breast surgery author year prevalence time Jamison 1979 44% 2 years Kroner 1989 23% 1 year Vecht 1990 18% 6 months Polinsky 1994 22-32% mean 8 years Tasmuth 1995 >50% 1 year Wallace 1996 22-49% 1 year Smith 1999 43% 6 years Johansen 2000 15% 6 years Fassoulaki 2002 33% 3 months Reuben 2004 50% 6 months Fassoulaki 2005 57% 6 months Kairaluomma 2006 8% 1 year Burton 2007 50% 1 year Hofso 2012 50% 1 year
New Definition Old Macrea, BJA, 2008 New Pain, April, 2017 1. Pain after surgical procedure 1. Pain after a surgical procedure, or increases in intensity after a surgical procedure 2. Pain after 2 months 2. Pain after at least 3-6 months..with significant impact on Quality of Life 3. Exclude other causes of the pain 3. Exclude other causes of the pain 4. Exclude pre-existing causes 4. The pain is either a continuation of post surgery pain or develops after an asymptomatic period 5. The pain is either: i) localised to the surgical field ii) projected to the innervation territory of a nerve in the field
1. Pre-existing pain 2. Tumour involvement Classification of post mastectomy pain Osteo/rheumatoid arthritis Fibromyalgia Costo-chondritis Cervical radiculopathy Recurrence Metastasis Cervical radiculopathy due to tumour 3. Post-surgical Intercostobrachial neuralgia Other neuralgias Persistent acute pain Scar pain Phantom breast Intercostal neuromas 4. Neuropathic 5. Pain due to implants & reconstruction 6. Other causes Carpal tunnel syndrome Radiation induced plexopathy Transient brachial neuritis Complex regional pain syndrome Capsulitis Capsular contraction and hardening Foreign body reaction Referred pain Implant migration Atypical chest pain syndrome Reconstruction issues Psychological factors Lymphoedema Pericapsulitis Muscle spasm Shoulder pain Post-chemo Post- radiotherapy Idiopathic Myofascial pain dysfunction syndrome
How big a problem is it? In a population of chronic pain patients..how many had pain as a result of surgery? Crombie et al, Pain 1998 5,000 chronic pain patients 23% = CPSP (high proportion with disability) How many people with acute pain go on to get pain at 1 year? Hayes et al, Acute Pain 2002 5,000 patients undergoing surgery Acute neuropathic pain 2% Feature= high intensity 9/10 Follow up Hayes et al, Acute Pain, 2002 Pain at 6 months, 78% Pain at 1 year, 56% 26 million operations / year in USA (2008) 1% of all patients develop CPSP (Katz, 2011)
Clarke et al., British Medical Journal, 2014 What this study adds 3% of patients, who had not used opioids previously, continued to use them for more than 90 days after major elective surgery Important public health concern because millions of patients undergo major surgery every year
Risk factors.. 1. Causal/ Modifiable Risk factors (Katz, Anesth & Analg, 2011) Acute pain Pre-existing pain? Psychological factors
2. Correlated risk factors (Katz, Anesth & Analg, 2011) Younger age Gender? Psychological distress? Pain
Risk factors 1. Patient related 2. Surgery related
Patient-related risk factors pain predicts pain Preoperative pain (Forsythe, 2008) Intensity of acute pain (Masselin-Dubois, 2013) Acute neuropathic pain (Haroutiounian, 2013) High opioid consumption perioperatively (Kalso, 2001) Pain in other body parts (Pinto, 2012) Younger age (Masselin-Dubois, 2013) Female (Ochroch, 2006)
Psychological risk factors Pre-op anxiety and catastrophizing: meta analysis (2x likelihood of developing CPSP (Theunissen, Clin J Pain, 2012) Depression (Attal, 2014) Catastrophizing (Masselin-Dubois, 2013) Sensitivity to pain traumatisation (Page 2013) Anxiety (Kleimann, 2011) Fear of long term consequences of surgery (Peters, 2007)
Surgical risk factors Low vs. high volume surgical unit, 13% increase in risk of CPSP (Tasmuth,1999) Duration of surgery (Kalso, 2007) Minimally invasive surgery (Grant, 2004) Stitch types (Cerfolio, 2003) Nerve damage, preservation (Jensen, 1985)
Predictive factors for chronic pain after breast surgery Anderson et al, Pain, 2015, n=575 Pain at 1 year: Moderate- severe post op pain (5.0) Axillary lymph node with ICB nerve preservation (3.0) Neuropathic pain @ 1 week (1.8) Age < 65 (1.8) Wang, Canadian Medical Assoc Journal, 2016 Young age Axillary lymph node dissection Acute pain High quality evidence showed no association with: BMI Type of breast surgery Chemotherapy Reconstruction
Clinical Prediction Model and Tool for Assessing Risk of Persistent Pain After Breast Cancer Surgery Tuomo J. Meretoja, Kenneth Geving Andersen, Julie Bruce, Lassi Haasio, Reetta Sipilä, Neil W. Scott, Samuli Ripatti, Henrik Kehlet, and Eija Kalso March 2017
Risk Factors what can we discuss with surgeons? Information for patients Pre-assessment / pain clinic Pre-op anaesthetic strategies / algorithms /PVB Surgical technique (!) (e.g. mesh, preservation of nerves, minimally invasive etc.) Enhanced recovery e.g. Kehlet et al, Br J Surgery, 2005, Fast Track Surgery Pain clinic follow up
Pathophysiology what is it about pain that causes more pain?..transition to chronicity. 1. Nociceptive inflammation, ischaemia, oedema, pressure, traction 2. Neuropathic peripheral & central sensitisation spinal cord neuroplasticity neuroma 3. Psychological & social 4. Genetic
The neuropathic component in persistent pain after surgery; systematic review Haroutiunian, PAIN, 2013 CPSP after 11 types of surgery Amount of pain depends on likelihood of nerve damage Neuropathic pain in 65% of thoracotomy patients 33% groin surgery 6% knee surgery
Post surgical breast pain Jung, PAIN 2003 1. Intercostobrachial neuralgia 2. Other nerve injury 3. Neuroma 4. Phantom breast
Natural History Long-term follow-up of breast cancer survivors with postmastectomy pain syndrome Macdonald, et al, British J of Cancer, 2005 Persistent pain after breast surgery: 6-year nationwide follow up Mejdahl, Kehlet et al, BMJ, 2013 1996. 43% pain @ 3 years 2002..21% pain @ 9 years 2008.47% pain @1 year 2013.37% pain @ 6 years
Treatment - prevention.from Pre-emptive Analgesia (blocking preoperative stimuli).to Preventative Analgesia (blocking noxious stimuli / central sensitisation across the entire perioperative period)
Preventative treatments 1. Nerve blocks / Regional 2. Drugs
Regional anaesthesia to prevent chronic pain after surgery: a Cochrane systematic review and meta-analysis M. H. Andreae 1,* and D. A. Andreae 2 BJA, 2013 23 RCT s Epidural anaesthesia and paravertebral blocks may be effective in preventing chronic pain at 1 year Effective in about 1 in 4 patients treated
Preincisional Paravertebral Block Reduces the Prevalence of Chronic Pain After Breast Surgery Kairaluoma et al, Anesth Analg 2006;103:703-708 Preincisional paravertebral block provides significant immediate postoperative analgesia In the same patients (n = 60), @12 months, sig less pain in the PVB group In addition to providing acute postoperative pain relief, preoperative PVB reduces the prevalence of chronic pain 1 yr after breast cancer surgery.
Epidurals Intraoperative epidural analgesia provides preventative analgesia in abdominal surgery Lavand homme et al, Anaesthesiology 2005 Clear benefit of epidural in preventing chronic pain @ 1 year Intraoperative epidural better than postoperative epidural Effective epidural better than effective parenteral only analgesia @ one year
Systematic review of therapeutic interventions to reduce chronic post surgical pain (32 RCT s) Humble et al, European J of Pain (2015) POSITIVE Gabapentinoids Lidocaine iv lidocaine, EMLA Regional TIVA NEGATIVE Ketamine Cryoanalgesia Local anaesthetic infiltration Remifentanil (increased chronic pain)
1. Gabapentin around time of surgery no effect on chronic pain POSITIVE Meta analysis (Clarke, 2012) 4/8 RCT s, positive effect at 2 months NEGATIVE Cochrane Systematic Review (Chaparro, 2013) 280 patients analysed, pain at 6 months No effect RCT, Gabapentin 1200mg prior to Thyroidectomy Sig less pain at 3 months (Brogley, 2008) RCT, Gabapentin vs Placebo Knee replacement No effect on chronic pain (Clarke, 2014)
2. Pregabalin around time of surgery Not a recommended treatment, can cause post operative somnolence Positive Meta-analysis of 3 studies (Clarke, 2012) All showed improvement in pain 2 RCT s.very large decrease in CPSP (p=0.007) Cochrane Systematic Review (Chaparro, 2013) 2/5 RCT s, significant benefit Negative 3 unpublished RCT s from Pfizer (2010-2014).all negative for acute and chronic pain i) 307 patients undergoing knee replacement ii) 501 patients, hysterectomy iii) 425 patient, hernia Systematic review (Martinez, May 2017) No difference between pregabalin and placebo @ 3 months Use for acute pain in pro-nociceptive surgery Side effects a problem
Multimodal analgesia Standard protocols, now widely used e.g. Paravertebral blocks at MD Anderson Pre-assessment clinic: screening for pain / psychological factors / pain catastrophising scale.genetic screening tests? Education : patients, surgeons, anaesthetists, nurses, psychologists
General treatment strategies for chronic postsurgical neuropathic pain Preventative Perkins & Kehlet, Anesthesiology 2000 Surgical procedure, preservation, sentinel node biopsy Better postoperative pain management Informed consent / preparatory information Established Dworkin, Archives Neurol 2003: 60; 1524 Amitriptyline Gabapentin Opioids Tramadol 5% Lidoderm patch, EMLA
Positive therapies for Prevention of PSBP 1. EMLA, applied to chest wall prior to surgery, less pain @ 3 months 2. Venlafaxine XR 70mg, before and for 2 weeks post surgery,no diff acute pain, significantly less chronic pain @ 6 months 3. Aggressive acute pain management 4. Preincisional paravertebral block 5. Multimodal analgesia with gabapentin, EMLA, ropivacaine, less acute pain & pain @ 6 months Fassoulaki, 2000 Reuben, 2004 Iohom, 2006 Kairaluoma, 2006 Fassoulaki, 2005
A pain management programme for chronic cancertreatment-related pain. Robb, Williams, Duvivier, Newham Journal of Pain 2006:7;75-150 Theory of cancer-related pain Pain pathways Over/under activity cycle Pacing Exercise and fitness TENS Posture and manual handling Relapse and prevention
Psychology interventions Goal setting Role of factors involved in pain Homework assignments Relaxation techniques Cognitive skills Relapse and prevention
Results significant (p<0.05) improvements in: Pain severity Psychological distress Pain & psychological coping indices Activities of daily living General fitness
Research Proposal Exercise to prevent shoulder conditions in patients undergoing breast cancer treatment Aim: to conduct a randomised controlled trial (RCT) supported with qualitative research, to investigate the clinical and costeffectiveness of early supervised exercise on outcomes of arm function, chronic pain and quality of life at one year in women undergoing treatment for breast cancer.
Intervention A physiotherapy-led structured exercise programme, incorporating behavioural strategies and monitoring to encourage adherence. A minimum of 4 face-to-face specialist treatment sessions with individual participants will be delivered within 12 weeks of surgery. Access to interim telephone support will be provided. The programme will restrict to controlled early stretching and ROM exercises, with subsequent progression to maintain strength and function (weeks 2 to 12). Qualitative interviews will be used during the feasibility phase of the trial to explore acceptability of to the intervention.
Outcomes arm, shoulder and hand function at 12 months using the 30-item Disability Arm Shoulder Hand (DASH) questionnaire quality of life Functional Assessment of Cancer Treatment-Breast (FACT-B) Short-Form-12 and EQ-5D-5L. Data on postoperative adverse events, surgical site infection and healthcare resource use will be collected at 6 and 12 months after surgery.
Positive therapies for Prevention of PSBP 1. EMLA, applied to chest wall prior to surgery, less pain @ 3 months 2. Venlafaxine XR 70mg, before and for 2 weeks post surgery,no diff acute pain, significantly less chronic pain @ 6 months 3. Aggressive acute pain management 4. Preincisional paravertebral block 5. Multimodal analgesia with gabapentin, EMLA, ropivacaine, less acute pain & pain @ 6 months Fassoulaki, 2000 Reuben, 2004 Iohom, 2006 Kairaluoma, 2006 Fassoulaki, 2005
Current Treatment Paradigms The Toronto General Hospital Transitional Pain Service: development and implementation of a multidisciplinary program to prevent chronic postsurgical pain (Katz, J Pain Res, 2015) Nurse navigator Psychologists (ACT)
Clinical Manifestations our approach to the patient with CPSP Type of pain? Cause? Exclude other causes (infection, recurrence) Psychological and social factors Temporal Context? Electronic Patient Record
Future Directions Identify, Causative / Modifiable risk factors vs. Associative risk factors Measure psychological variables Genetic assays to identify genes controlling the variability in developing chronic pain Aim is to identify susceptibility to chronic pain and sensitivity to analgesics Chronic pain heritability is variable
Conclusions 1 year incidence = 0.5-1.0% Avoid pain before during and after surgery translate advances in acute pain to chronic setting Psychological pre-assessment Education / discussion with patients / surgeons In some cases preventive analgesia may be beneficial Transitional Pain Service.tracking..database Pragmatic approach All diseases have an acute phase Drugs good for acute pain must be good for chronic pain