key concepts in acute pain management - 1 surgery residents dec. 15, 2009
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KEY CONCEPTS IN ACUTE PAIN MANAGEMENT - 1 SURGERY RESIDENTS Dec. 15, 2009. John Penning MD FRCPC Director Acute Pain Service. Objectives. Define consequences of acute pain Explain the rationale for cyclo-oxygenase inhibitors as foundational analgesics - PowerPoint PPT PresentationTRANSCRIPT
KEY CONCEPTS IN ACUTE PAIN MANAGEMENT - 1SURGERY RESIDENTS Dec. 15, 2009
John Penning MD FRCPC
Director Acute Pain Service
Objectives
Define consequences of acute pain Explain the rationale for cyclo-oxygenase
inhibitors as foundational analgesics Concerns with NSAIDs and Coxibs Limitations of T#3 Tramacet a “me too” or something new? Rational multi-modal orders for the routine,
uncomplicated patient
Consequences of poorly managed acute post-operative pain
The Patient suffers– Pathophysiological consequences
• See PGY-1 lecture– Psychological:
• Anxiety, Depression, Fatigue, Sleep Deprivation
– Chronic Post-surgery/trauma Pain• Are some patients at more risk?• Can we do anything to prevent it?
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
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– limit S/E and complications from our
analgesic therapies
What is the “Best Way” to manage acute post-operative pain?
FIRST, DO NO HARMTherefore, the “best way” is a BALANCE
Patient Safety
Effective AnalgesicModalities
Analgesia with Opioids alone The harder we “push” with single mode analgesia, the
greater the degree of side-effects
Analgesia
Side-effects
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.”
Analgesia
Side-effects
KEY POINTS There is as of yet no single silver bullet!! Acetaminophen limited efficacy NSAIDs or Coxibs still limited efficacy and
some significant adverse effects Opioids efficacy is limited by side-effects
– The Opioid Side-effect Burden Multi-modal Analgesia
– Attain analgesic goals– Avoiding S/E
Goals of Multi-Modal Analgesia
Attain analgesic goals1. VAS – 3 /10 at rest and 5/10 with activity
2. Pain is not limiting patient’s rest/activity
3. Patient satisfaction
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
Cyclo-oxygenase inhibitors NSAIDs/Coxibs and AcetaminophenCONCEPT # 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 %
The problem with the “Little Pain – Little Gun”, “Big Pain – Big Gun” Approach
With opioids analgesic efficacy is limited by side-effects
– You can get some of the people comfortable some of the time BUT!,
You can’t get all of the people comfortable all of the time.
The problem with the “Little Pain – Little Gun”, “Big Pain – Big Gun” Approach
Important rationale for COX-Inhibitors in management of severe acute pain
– Patient Safety!! If the “Big Gun” is failing due to dose limiting sedation/respiratory depression, the addition at that time of the “Little Gun” may kill the patient.
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
PCA morphine started in PACU, plus nurse supplements totaled 26 mg in 90 minutes
Still c/o pain, 30 mg ketorolac IM 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
Gain control of acute pain with fast onset, short acting opioid(fentanyl)
Add NSAID adjunct early Monitor closely for sedation and respiratory
depression after pain is alleviated by any means
Mortality From NSAID-Induced GI Complications vs Other Diseases in US
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Wolfe MM: NEJM 1999; 340: 1888-99
Penning’s Pessimistic Policy on Pain Pills Pick your “Poison” Pursuant to Patient
Profile
COX-inhibitors are potential killers “in the long run”
Opioids are potential killers “in the short run” But they can still get you in the long run
Cyclo-oxygenase inhibitors
Acetaminophen
NaproxenCelecoxib
Ketorolac
Rofecoxib
Cell Membrane Phospholipids
Arachidonic Acid
Phospholipase
Prostaglandins Prostaglandins
Gastric ProtectionPlatelet Hemostasis
Acute PainInflammationFever
COX-2 COX-1
Why a COX-2 inhibitor?
Equivalent analgesic efficacy with non-selective COX-inhibitors
No effects on platelets!
Better GI tolerability– Less dyspepsia, less N/V
Two hours before surgery associated with post-op pain
1. Celecoxib 400 mg PO If severe allergy to sulfa?
2. Naproxen 500 mg PO Contra-indications to NSAID
Acetaminophen 1000 mg PO
First on and Last Off
Celecoxib 200 mg Q12 H Ibuprofen 400 mg Q4H
– OTC 200 mg capsules Naproxen 375 mg Q8H
– OTC “Aleve” 220 mg capsules (box warning max of 3 per day)
Acetaminophen may be combined with NSAID or Coxib– 650 mg Q4H, OTC – Tylenol Arthritis LA 650 mg per tablet
• 1300 mg Q8H• Caution against other acetaminophen products
Contra-indications to Celecoxib/NSAIDs
Patients with the “ASA triad”– Chronic Nasal polyps who after ASA gets– Exacerbation of asthma– Angioedema of upper A/W
Not a true IG “E” type allergy There may be a cross reactivity with cox-
inhibitors COPD or asthma alone not a contra-
indication to NSAIDs or Coxibs
Celecoxib and “sulfa allergy” Allergy to sulfa?? History, Please!
– Most 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
Risk of renal failure with NSAIDs/Coxibs
Renal insufficiency or risk there of – especially if risk of hypovolemia periop– 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
Terrible triad for GFR– Hypovolemia, ACE/ARB and NSAIDs
Prostaglandins Vasodilation increased flow
Angiotensin 2 Vasoconstriction Decreased flow
Contra-indications to Celecoxib/NSAIDs
Active peptic ulcer disease Congestive heart failure
– Definite risk of fluid/sodium retention– Risk of thrombosis??
DrugSummary Relative Risk for Cardiovascular Event (95% CI)
Rofecoxib, ≤ 25 mg
1.33 (1.00 - 1.79)
Rofecoxib, > 25 mg
2.19 (1.64 - 2.91)
Celecoxib 1.06 (0.91 - 1.23)
Diclofenac 1.40 (1.16 - 1.70)
Naproxen 0.97 (0.87 - 1.07)
Piroxicam 1.06 (0.70 - 1.59)
Ibuprofen 1.07 (0.97 - 1.18)
Meloxicam 1.25 (1.00 - 1.55)
Indomethacin 1.30 (1.07 - 1.60)*CI indicates confidence interval.
Source: JAMA. Published online September 12, 2006 (McGettigan and Henry).
Tissue healing issues with NSAIDs and Coxibs??
Risk of non-union in bone surgery or non-fusion in spine surgery– COX-1 proven a problem in high doses– Coxibs no definitive data
Risk of dehiscence of colon anastomosis increased from 4% to 18% with ketorolac, diclofenac, celecoxib– Very controversial– Currently TOH refraining from NSAIDS in this
population – examining data
Codeine Myths that still prevail!
Codeine is a “weak” opioid?
Codeine is inherently safer than the more potent opioids?
Who still uses Tylenol # 3 ?
WHY ??
Who still uses Tylenol # 3 ?
Prescribe over the phone Only modest risk of diversion relative to
straight potent opioids – Avoid putting hydromorphone, morphine
into community Break and enter risk with Oxys Codeine effective for diarrhea, cough
Codeine, Ultrarapid-Metabolism Genotype, and Postoperative DeathNEJM August 20, 2009 pp 827-828
Healthy 2 yr. boy 13 kg with OSA went for adenotonsillectomy
10 – 12.5 mg of codeine with 120 mg acetaminophen PO Q4 – 6 H prn found unresponsive a.m. of day 3 after surgery
Toxic morphine levels in blood
CODEINE – A drug whose time has come and gone?
N Engl J Med 351; 27 Dec. 30, 2004
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
GeneticVariability And drug interactions1% Finland
10% Greek30% East Africa
Potential Codeine Drug Interactions
Major pathway – CYP3A4– Inducers decrease codeine effect– Inhibitors increase codeine effect
Minor pathway - CYP2D6– Inducers increase codeine effect– Inhibitors decrease codeine effect
Inhibitors of CYP2D6
SSRIs (potent) especially PAXIL Cimetidine, Ranitidine Desipramine Propranolol Quinidine (potent) Viagra Many anti-biotics and chemo
Why not just go with Percocet?
Too potent for some patients– 5 mg oxycodone = 60 mg codeine
It too, may be a pro-drug?– Codeine is to Morphine as – Oxycodone is to ??
Oxymorphone– The jury is still out on this one
Instead of Tylenol # 3 ? Acetaminophen 650 mg PO Q4H
with Morphine 10 – 20 mg PO Q4H prn
OR
Dilaudid 2 – 4 mg PO Q4H prn
Newly available Tramacet 1 – 2 tabs PO Q4H prn
Opioids: Rational multi-route orders?
Foundation of Acetaminophen/NSAID
Morphine 5 - 10 mg PO Q4h prn Morphine 2.5 - 5 mg s.c. Q4h prn Morphine 1-2 mg IV bolus Q1h prn
Hydromorphone 1 - 2 mg PO Q4h prn Hydromorphone 0.5 – 1 mg s.c Q4h prn Hydromorphone 0.25 – 0.5 mg IV Q1h prn
Towards a better analgesic for acute pain High level of efficacy A good drug would have an inherent
multi-modal mechanism of action Very low risk of serious side-effects Low incidence of bothersome side-
effects Very limited abuse potential Affordability
TRAMADOL
What about Tramacet?
Combination drug, 325 mg of acetaminophen + 37.5 mg of tramadol
Ordered like T#3– 1 to 2 tabs Q4H prn
Efficacy limited by max dose for acetaminophen.
Opioids can be added as required!
Tramacet - How does it work?
Inherent multimodal action – 4 distinct mechanisms
1. acetaminophen2. Weak mu agonist – very weak opioid3. Augments endogenous inhibitory nociceptive
modulation via serotonin 4. and norepinephrine pathways
Advantages of Tramacet?
Tramadol’s “strength” lies in it’s “weakness” as an opioid– Poor Mu receptor affinity
Minimal opioid effect– Less constipation, faster return to normal
bowel function– Less N/V– No sig. respiratory depression– No sig. risk for abuse (not classified as
narcotic)
Advantages of Tramacet? Tramadol’s “strength” lies in it’s
“weakness” as an opioid– Poor Mu receptor affinity
Tramadol does not antagonize the action of classic mu agonists like morphine, dilaudid or fentanyl– Unlike the partial agonist/antagonists such as
Talwin, Nubain, Stadol
Other mu agonist may be added
Why combination analgesics are not a great idea
Acetaminophen-Induced Acute Liver Failure: Results of a USA Multicenter, Prospective Study. Hepatology, Vol. 42, No. 6, 2005. Larson et al.
22 centers, 662 cases ’98 – ’03. 50% cases due to acetaminophen 50% of acetaminophen cases inadvertent
Tramacet Precautions Serotonergic Syndrome
– Patients may be at risk if Tramacet is co-administered with other serotonin increasing drugs
• MAO inhibitors, meperidine• SSRI and SNRIs (cymbalta), TCAs, Trazodone• SR Tramadol; Ultram, Tridural, Relivia
– Spectrum of severity• Mental changes: confusion, agitation• Automonic effects: fever, sweating, labile vitals• Motor effects: pyramidal rigidity, tremors• Supportive treatment
What about Codeine allergy? Is it safe to give Tramacet?
Product Monograph states: “Patients with a history of anaphylactoid reactions to codeine and other opioids may be at increased risk and therefore should not receive Tramacet.
Very cautious position, no evidence Morphine and it’s cousins much more likely to
be of concern in severe codeine allergy. DO A HISTORY! 99% of patient reported
codeine allergy are just S/E or MBE.
CODEINE MORPHINE
OXYCODONE TRAMADOL
Tramadol Fentanyl
Meperidine
Tramacet Cost? Hospital gets a deal. Price matched with T # 3.
Patient pays 62 cents per tab.
Dispensing fee $15.00 + 60 tabs = $52.00 vs. about $18.00 for T#3.
Discuss with patient?
Acute Pain Treatment for the Ambulatory Patient Pre-op: 2 hours before
– Celecoxib 400 mg or Ibuprofen 600 mg– Acetaminophen 975 mg or Tramacet 2 –3
Intra-op– Bupivacaine 0.5% epi, 0.5 ml/kg surgical wound
infiltration, pre-incision better Post-op
– Acetaminophen 650 – 975 mg Q6H– Naproxen 375 mg Q8H – Hydromorphone 1 or 2 mg tabs, 1 – 2 tabs Q4HOR– Ibuprofen or celecoxib/Tramacet/Hydromorphone
Ordering the Analgesic Ladder?
Acetaminophen 650 mg PO Q4H prn Tramacet 1 – 2 tabs PO Q4H prn Hydromorphone 2 – 4 mg PO Q4H prn
– Reduce to 1 -2 mg in elderly Hydromorphone 1 – 2 mg s.c. Q4H prn
The Analgesic Titration Tree
A
A A
A
A
A A
A
A
TT
T T TT
T
T TD
D
Acetaminophen 325 mg
Tramacet
Hydromorphone 2 mg
Foundation of NSAID or Coxib
Tramacet “titration” algorithm
Tramacet 2 tabs PO Q4H straight W/A– If pain is < 3/10 with activity and no
hydromorphone in last 4 hours, may hold 1 or 2 tabs of Tramacet and replace with 1 or 2 tabs of acetaminophen accordingly
– If pain > 5/10 with activity may supplement Tramacet with hydromorphone 1- 2 mg PO or 0.5 – 1 mg s.c. Q4H prn
Ordering the Analgesic Ladder?
Foundation of NSAID or Coxib
Acetaminophen 2 tabs
Acetaminophen 1 tab + Tramacet 1 tab
Tramacet 2 tabs
Tramacet 2 tabs + HM 2 mg
The TOH ATH Analgesic Ladder
Foundation of NSAID or Coxib
Acetaminophen 2 tabs
Acetaminophen 1 tab + Tramacet 1 tab
Tramacet 2 tabs
Tramacet 2 tabs + HM 2 mg
Acute Pain Lecture # 2
The more challenging patient with acute pain– Opioid tolerant, acute on chronic pain– How are they different?– Role of anti-pronociceptive agents
Fundamentals of IV PCA What the surgeon needs to know about
neuraxial opioids, epidurals
Useful texts
Free!! From Canadian Pain SocietyManaging Pain: The Canadian Healthcare
Professional’s Reference. Edited by Roman Jovey. 2008.
Endorsed by the CPS. Order from Purdue Pharma
Acute Pain Management: A practical guide. 3rd ed. 07
Pamela MacIntyre. Saunders/Elsevier
http://www.anzca.edu.au/publications/acutepain.pdf
The above web site has the entire document and is freely Available to download.
ACUTE PAIN MANAGEMENT:SCIENTIFIC EVIDENCE 2nd Edition June ‘05Australian and New Zealand College of AnaesthetistsAnd Faculty of Pain Medicine.
Useful websites on Pain
Prospect:Procedure Specific Post-op Pain Management
http://www.postoppain.org/frameset.htm Pain Explained
http://www.painexplained.ca/content.asp?node=4 The Canadian Pain Society
http://www.canadianpainsociety.ca/indexenglish.html
Useful websites on Pain
Pain Institute http://www.medscape.com/infosite/paininstitute/article-5?src=0_0_ad_ldr Internation Association for the Study of Pain
http://www.iasp-pain.org//AM/Template.cfm?Section
=Home