KEY CONCEPTS IN ACUTE PAIN MANAGEMENTPGY-1 Faculty of MedicineUniversity of Ottawa Feb.18, 2009 John Penning MD FRCPC Director Acute Pain Service The Ottawa Hospital
Objectives • General Key Concepts • The “real cost” of acute pain • Multi-modal analgesia • New Dimensions in pain management • How and when to use naloxone
Objectives • Discuss key concepts of each modality • COX-inhibitor as Foundational analgesic • Tylenol # 3 has it’s limitations • Opioids? – think outside the “box” • Tramacet – a “me too” drug? Or something new to add? • Anti-pronociceptive agents for difficult acute pain
Consequences of poorly managed acute post-operative pain • The Patient suffers • CVS: MI, dysrhythmias • Resp: atelectasis, pneumonia • GI: ileus, anastamosis failure • Endocrine: “stress hormones” • Hypercoagulable state: DVT, PE • Impaired immunological state • Infection, cancer, wound healing • Psychological: • Anxiety, Depression, Fatigue, Sleep Deprivation • Chronic Post-surgery/trauma Pain
Consequences of poorly managed acute post-operative pain • The Hospital • Increased costs $$$ • Poor staff morale • Reputation/Standing in the Community, Nationally • Accreditation • Canadian Council on Health Services Accreditation; Acute Care Standard 7.4 2005. • TOH Pain Management Council 2006 • TOH Pain Assessment and Management Policy ADM 8 • Litigation
Consequences of poorly managed acute post-operative pain • The Healthcare professional • Morale • Complaints to College • Litigation
Risk Factors for severe post-op pain • While incision size and type of surgery are predictors of post-op pain, the greatest source of variability is the PATIENT. • Younger age • Female • Pre-operative pain issues • Anxiety, depression, catastrophizing
Chronic Post-Surgical PainRisk Factors • Brandsborg B. et al. Risk factors for chronic pain after hysterectomy. Anesthesiology 2007; 106: 1003 – 12. • Pre-operative pelvic pain as the main indication for surgery • Pain problems elsewhere • Previous C/S • Procedure done with spinal anesthesia shown to decrease incidence of CPSP.
The New Challenges in Managing Acute Pain after Surgery and Trauma • Patients/Society more “aware” of their rights to have good pain control • We are being held accountable • Pressure from hospital to minimize length of stay • Control pain, yet limit the side-effect burden and complications secondary to opioids
The New Challenges in Managing Acute Pain after Surgery and Trauma • The Opioid Tolerant Patient • The greatest change in practice/attitudes in the last 10 years is the now wide spread acceptance of the use of opioids for CHRONIC NON-MALIGNANT PAIN • Renders the “usual” standard “box” orders totally inadequate in these patients • Get an accurate Pain/Analgesic History • The Brief Pain Inventory – “BPI”
Brief Pain Inventory: Charles Cleeland
What is the “Best Way” to manage Acute Pain? • FIRST, DO NO HARM Therefore, the “best way” is a BALANCE Effective Analgesic Modalities Patient Safety
Analgesia with Opioids alone • The harder we “push” with single mode analgesia, the greater the degree of side-effects Side-effects Analgesia
Case Problem: Severe Respiratory Depression after Ketorolac? • Healthy 34 yr. patient c/o severe incisional pain in PACU after ovarian cystecomy • Received 200 g fentanyl with induction and 10 mg morphine during case, no foundational analgesic given • PCA morphine started in PACU, plus nurse supplements totaled 26 mg in 90 minutes • Still c/o pain, 30 mg ketorolac IV, given with some relief after 15 minutes, so patient sent to ward • 60 minutes later found unresponsive, cyanotic, RR 4/min.
Case Problem: Severe Respiratory Depression after Ketorolac? • Pharmacodynamic drug interaction between morphine and NSAID • morphine’s respiratory depressant effect opposed by the stimulatory effects of pain, busy PACU environment • NSAID decreases pain, morphine’s effect unappossed
Case Problem: Severe Respiratory Depression after Ketorolac? • Safer approach? • Add NSAID foundational analgesic ASAP • Gain control of acute pain with fast onset, short acting opioid(fentanyl) • In a patient previously “loaded” with opioids and c/o pain despite some sedation, Monitor closely for over-sedation and respiratory depression after pain isalleviated by any means!
The problem with the “Little Pain – LittleGun”, “Big Pain – Big Gun” Approach • With opioids analgesic efficacy is limited by side-effects • “Optimal” analgesia is often difficult to titrate • 10 – fold variability in opioid dose : response for analgesia • A dose of opioid that is inadequate for patient A can lead to significant S/E or even death in patient B. • Many patient factors add to the difficulty • Opioid tolerance, anxiety, obstructive sleep apnea, sleep deprivation, concomitantly administered sedative drugs
Multi-modal Analgesia • “With the multimodal analgesic approach there is additive or even synergistic analgesia, while the side-effects profiles are different and of small degree.” Side-effects Analgesia
Pain Pathways There is as of yet no single silver bullet!!
Acute Pain Management Modalities • Cyclo-oxygenase inhibitors • Non-specific COX inhibitors(classical NSAIDs) • Selective COX-2 inhibitors, the “coxibs” • Acetaminophen is probably COX-3 • Local anesthetics • Opioids • NMDA antagonists • Ketamine, dextromethorphan • Anti-convulsants • Gabapentin, Pregabalin
NSAID, Coxibs and Acetaminophen CONCEPT # 1 The foundation of all acute pain Rx protocols. ”First on last off” • sole agent in mild /moderate pain • Analgesic efficacy is limited inherently • In contrast, with opioids efficacy is limited by S/E • Opioids added as required • opioid sparing effect 30-60 %
COX-INHIBITORS vs. OPIOIDS • Efficacy Limited InherentlyLimited by S/E • Inter-patient dose variability SmallLarge, making dose titration difficult • Life threatening complications Upper GI bleedingResp. depression With chronic useRisk is early
COX-INHIBITORS vs. OPIOIDS • Toxicity, S/E Tissue/organ toxicneurologic dysfunc • Drug tolerance Not evidenttolerance is part of normal response • Abuse potential Nil Yes
Cyclo-oxygenase inhibitors Acetaminophen Naproxen Celecoxib Ketorolac Numerous others
Cell Membrane Phospholipids Phospholipase Arachidonic Acid COX-2 COX-1 Prostaglandins Prostaglandins Acute Pain Gastric Protection Inflammation Platelet Hemostasis Fever
Why a COX-2 inhibitor? • No effects on platelets! • Better GI tolerability • Less dyspepsia, less N/V • Equivalent analgesic efficacy with non-selective COX-inhibitors
Celecoxib and “sulfa allergy” • Allergy to sulfa?? History, Please! • Most reported allergies are bogus: N/V, diarrhea • A rash with sulfonamide anti-biotics? Celecoxib belongs to the “other” class of sulfonamides: furosemide, glyberide, etc. • Do not use celecoxib is history of anaphylaxis or severe cutaneous reaction (Steven-Johnson sydrome. etc.) with a sulfonamide
Two hours before surgery associated with post-op pain • Celecoxib 400 mg PO If severe allergy to sulfa? OR • Naproxen 500 mg PO Contra-indications to NSAID? Plus Acetaminophen 1000 mg PO
Contra-indications to Celecoxib/NSAIDs • Patients with the “ASA triad” • Risk of severe asthma, angioedema precipitated with COX-inhibitor • Renal insufficiency or risk there of • especially if risk of hypovolemia periop • Patient on ACE inhibitors or ARBs • Vascular patients having aortic cross-clamp and/or probable angiogram peri-operatively • Poorly controlled hypertension • Especially if pt. is on ACE inhibitor, potent loop diuretics
Contra-indications to Celecoxib/NSAIDs • Congestive heart failure • Fluid/sodium retention • Active peptic ulcer disease
The Opioids • We have to stop trying to put every patient in the “analgesic dose box” Meperidine 75 mg IM Q4H prn Tylenol #3 1 – 2 PO Q4H prn
Opioids CONCEPT # 2 Pharmacokinetic + Pharmacodynamic patient to patient variability results in 1000% variability in opioid dose requirements (standardized procedure, opioid naïve patient) • opioid dosage must be individualized • therefore, if parenteral therapy indicated, IV PCA much better suited to individual patient needs than IM/SC
True or False? • One opioid is just like any other, in terms of analgesic efficacy and side-effects.
Opioids – Are they all the same? • Morphine • Hydromorphone (dilaudid) • Fentanyl • Oxycodone (parenteral n/a) • Meperidine (demerol)
Opioids – Do they all act the same? • Opioids work as analgesics by activating endogenous inhibitory pain modulating systems • Opioid receptors • Mu, Delta and Kappa • Large genetic variability in expression • Good choice in one patient may be poor choice in another • Analgesic efficacy • Side-effect profile
Meperidine Morphine Atropine Fentanyl Bupivacaine
Meperidine’s major problem • Normeperidine • The “ugly” metabolite • Neuroexcitatory: twitches, dilated pupils, hallucinations, hyperactive DTR, seizures • Non-opioid receptor mediated, no tolerance • Half-life is 15 – 20 hours N-demethylation
True or False? • One opioid is just like any other, in terms of analgesic efficacy and side-effects. • Answer. There is considerable variability between patients in response to different opioids.
Opioid Myths that still prevail! • Codeine is a “weak” opioid? • Codeine is inherently safer than the more potent opioids?
CODEINE – A drug whose time has come and gone? N Engl J Med 351; 27 Dec. 30, 2004
Problems with Codeine • 62 yr. male with CLL, presents with bilateral pneumonia. • Broncho-lavage revealed yeast • Anti-biotics: Ceftriaxone, clarithromycin, voriconazole • Codeine 25 mg PO TID for cough
Problems with Codeine • Day 4 became markedly sedated, pin-point pupils and ABG reveals PaCO2 of 80 mmHg. Marked improvement with Naloxone. • What’s the expected morphine blood level? • Answer: 1 to 4 mcg/L • This patient’s morphine blood level? • 80 mcg/L
Codeine Metabolism in Normal Circumstances • The major pathways convert codeine to inactive metabolites • CYP3A4 pathway yields norcodeine • Glucuronidation • The minor pathway, about 10%, yields morphine • CYP2D6, essential for analgesic effect 60 mg Codeine PO – approx. 4 mg morphine SC • Variability! 60 mg PO Codeine yields potentially 0 to 60 mg parenteral morphine
Genetic Variability And drug interactions 1% Finland 10% Greek 30% East Africa