Transcript key concepts in acute pain management

KEY CONCEPTS IN ACUTE
PAIN MANAGEMENT - 2
SURGERY RESIDENTS Jan. 8, 2008
John Penning MD FRCPC
Director Acute Pain Service
Objectives
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Review key concepts of each modality
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COX-inhibitor before opioid
Tylenol # 3 has it’s limitations
3rd dimension of analgesia “anti-pronociception”
Role of Pregabalin, Ketamine
Review principles discussed by case
presentation
– Opioid tolerance, conversion from IV to PO
– When, how to use naloxone
– Assessing the hypotensive epidural patient
The problem with the “Little Pain – Little Gun”,
“Big Pain – Big Gun” Approach
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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
NSAID and Acetaminophen
CONCEPT # 1
The foundation of all acute pain Rx protocols.
”First on last off”
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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 %
Acute Pain Management Modalities
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Cyclo-oxygenase inhibitors
– Non-specific COX inhibitors(classical NSAIDs)
– Selective COX-2 inhibitors, the “coxibs”
– Acetaminophen is probably COX-3
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Local anesthetics
Opioids
NMDA antagonists
– Ketamine, dextromethorphan
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Anti-convulsants
Alpha-2 delta sub-unit of VGCC
– Gabapentin, Pregabalin
Codeine Metabolism in Normal
Circumstances
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The major pathways convert codeine to
inactive metabolites
– CYP3A4 pathway yields norcodeine
– Glucuronidation
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The minor pathway, about 10%, yields
morphine
– CYP2D6, essential for analgesic effect
60 mg Codeine PO – approx. 4 mg morphine SC
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Variability! 60 mg PO Codeine yields
potentially 0 to 60 mg parenteral morphine
Instead of Tylenol # 3 ?
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Acetaminophen 650 mg PO Q4H
with
Morphine 10 – 20 mg PO Q4H prn
OR
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Dilaudid 2 – 4 mg PO Q4H prn
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Newly available
Tramacet 1 – 2 tabs PO Q4H prn
Case Problem:
32 yr. Male with multiple ribs #
Patient previously healthy, MVA with no other
injuries.
In Trauma Unit, c/o 9/10 pain. Difficultly
breathing due to severe splinting.
Analgesic orders are:
Morphine 5 – 10 mg PO / SC Q4H prn
Nurse just gave 5 mg PO one hour ago and
now won’t give anything for 3 hours!
What do you do?
Case Problem:
32 yr. Male with multiple ribs #
Review of PHx reveals no drug use.
Patient has received total of 24 mg
morphine in the 6 hours since
admission.
Case Problem:
32 yr. Male with multiple ribs #
Acetaminophen 650 mg PO Q4H W/A
Ketorolac 30 mg IV stat followed by 10
mg IV Q4H.
Morphine 10 – 15 mg s.c. Q4H
Morphine 2 - 3 mg IV Q1H prn
Ketamine 2.5 – 5 mg IV Q30 min. prn
NMDA Antagonists as “analgesics”
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Really anti-hyperalgesics, anti-pronociceptive
Central system of facilitatory pain pathways
that employ excitatory neurotransmitters
– Aspartate, glutamate
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Involved with central sensitization, Opioid
tolerance and Opioid Induced Hyper-algesia
NMDA antagonists block the facilitatory pain
pathways that induce “pathological” acute
pain
– Hyperalgesia, allodynia
NMDA Receptor Antagonists To prevent or reverse “pathological” acute pain
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Ketamine, Dextromethorphan
– Ketamine is widely known as a dissociative
“general anesthetic” - 3 mg/Kg IV bolus
– Ketamine 2.5 - 5.0 mg IV bolus for
analgesia in post-op patient – Ketamine as co-analgesic - combined 1:1
with morphine IV PCA. Better analgesia,
less S/E
– Dextromethorphan 30 mg PO Q8H
available OTC as Benylin DM, 3 mg/ml.
Case Problem:
32 yr. Male with multiple ribs #
IV PCA with morphine / ?ketamine
Ketorolac changed to naproxen when
eating. 250 mg PO TID
Or
Celecoxib 200 mg PO Q12H for 5 days
then 100 mg Q12H until no longer
needed.
Case Problem:
32 yr. Male with multiple ribs #
On day three patient is doing well and
planning for D/C tomorrow.
Convert to PO morphine.
Daily IV PCA use is 100 mg per day.
Equals about 200 mg per day orally.
Order about 50% as long acting.
60 mg MS Contin Q12H and 10 – 20 mg
PO Q4H prn.
Case Problem:
32 yr. Male with multiple ribs #
Weaning instructions:
As daily “breakthough” morphine requirements
decrease, reduce the MS Contin dose by
25% increments.
The NSAID or coxib is D/C after the opioids D/C
Acetaminophen is last to be D/C
Hyperalgesia
Pro-nociceptive modulation
Nociceptive
Stimulus
Anti-nociceptive modulation
Pain
Analgesia
Analgesic Drugs that act by
Nociceptive Modulation
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Pro-antinociceptive
– Augments inhibitory modulation of
nociception i.e opioids
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Anti-pronociceptive
– Inhibits the facilitatory modulation of
nociception i.e. ketamine, gabapentin and
pregabalin
Pregabalin for acute pain?
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Acute pain is “off-label” use
Be cautious of Over-sedation
– Sleep deprivation
– Elderly
– Patient already has significant opioids
Pregabalin:
The Good, The Bad and the Ugly
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The Good
– Chronic pain in region of surgery, when
pronociceptive mechanisms play a role such as
joint arthroplasty, bowel surgery in IBD patients,
chronic limb ischemic pain, opioid tolerant patients
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The Bad
– Mild pain when simple analgesics like
acetaminophen, NSAIDs or low dose opioid or
Tramacet suffice.
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The Ugly
– Too large a dose in sleep deprived patient already
in state of “morphine-failure”
Pregabalin dosage
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This is NOT a one size fits all.
– Drugs binding to receptors have
considerable patient to patient variability in
dose:response
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Alpha-2 delta sub-unit of Voltage-Gated
Calcium Channel
75 mg PO 2 hours pre-op (50 – 150)
50 mg PO Q8H for 3 to 5 days (25 – 75)
Naloxone, a two-edged sword!
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Is there a down side to the
administration of naloxone, 0.4 mg IV in
the post-op patient where opioid
induced respiratory depression is
suspected?
Severe acute pain, sympathetic
response, pulmonary edema, MI,
dysrhythmias
Case Presentation:
Somnolence and
hypoxemia while on IV PCA Morphine
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65 yr. Female with large ventral hernia repair
on IV PCA morphine
PMHx: Angioplasty 9 yr. ago, MI, CHF in past
– Moderate COPD, NIDDM
Doing well day 1, but day 2 found to be
somewhat confused, somnolent and SaO2
remains in high 80s despite Oxygen by N/P
Is Narcan Indicated? Urgently?
Case Presentation:
Somnolence and
hypoxemia while on IV PCA Morphine
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Further patient evaluation
– Patient arousable, RR 8-16, pupils slightly
constricted, BP 130/70, pulse 90 and reg.
– Chest: A/E fair bil. And some mild basilar creps
– ABG: pH 7.46 pCO2 50 pO2 55 BiCarb 36 FiO2 > .50
– Chest X-ray: Extensive bilateral, diffuse,
interstitial infiltrate consistent with ARDS
Naloxone would probably have had a serious
adverse effect on this patient. Hypoxemia despite
supplemental O2 in a breathing patient. Look
beyond the Opioids!
Case Presentation:
Somnolence and
hypoxemia while on epidural infusion of
hydromorphone/bupivacaine
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Management of suspected opioid induced
respiratory depression
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Support A/W
Simulate breathing
Supply supplemental oxygen
Assess SaO2, BP, Pulse
Naloxone titration, IF INDICATED
• 0.04 mg Q5 min. X 3 as needed
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Hypoxemia is a medical emergency
Hypercarbia is NOT
When a fast onset/short duration
opioid is required!
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Fentanyl 25 - 50 ug IV bolus Q 2 - 3 minutes
– onset in 30 seconds
– peak effect in 5 min. (30 min. with morphine)
– “short duration of action due to lipid solubility,
redistribution half-life is 15 minutes
– very potent respiratory depressant, give
supplemental Oxygen, monitor SaO2
– be very careful when benzodiazepines are also
administered ie. Versed
– Airway management skills/equipment available
– Naloxone
Opioids
Issue
With parenteral opioids the patient may experience intolerable side
effects before adequate analgesia is attained
Opioids
CONCEPT # 3
Targeted regional
administration of opioid
results in enhancement of
the therapeutic index (ratio
of analgesia/side effects)
Acute Pain Management Modalities:
Who Gets What and Why??
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Intrathecal morphine
– simple technique
– potent analgesia for 12 -16 hrs.
– highly effective for pain in lower abdomen
and lower limbs
– risk of delayed onset of respiratory
depresson
– C/S, Vag. Hyst., Rad. Prostatectomy,
Arthroplasty
What is an “EPIDURAL”?
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Anatomical
– Location of the catheter, C7 – L5
• Cervical, thoracic and lumbar epidurals
• Segmental Blockade
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Drugs
– Opioids (hydrophillic vs. lipophillic)
• morphine, hydromorphone, demerol, fentanyl
• Hydrophillic drugs migrate rostrally and also
yield greater spinal selectivity
What is an “EPIDURAL”?
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Drugs
– Local Anesthetics :
• Lidocaine, bupivacaine, ropivacaine
Varying concentrations/drug mass produces
“Differential Blockade”
sympathetics > somatosensory > motor
– Adjuncts: epinephrine, ketamine
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Mode of Drug Delivery
– Intermittent bolus vs. continuous infusions
True or False?
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Epidural analgesia impairs the
resolution of post-operative ileus i.e. it
“slows down the gut” delaying return of
normal bowel function.
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Epidural analgesia necessitates a foley
catheter until the epidural is removed
Epidural Pit-falls for the Surgeon
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Epidural hematoma
– > 50 reported cases in USA in patients treated
with LMWH
– Epidural insertion and removal of the catheter
– Risk factors: Elderly, low body weight, twice daily
dosing, anti-coagulation vs. prophylactic dose
range
The decision to fully anti-coagulate a patient with an
epidural in-situ should be made in consultation with
anesthesia and thrombosis medicine
Epidural Pit-falls for the Surgeon
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“Masked-Mischief”
– The potential high efficacy of the modality
could block pain related to complications
• Peritonitis; anastomosis dehiscence
• Wound infection, wound hematoma
• Limb ischemia, compartment syndrome
– Delay in appropriate therapy, diagnosis
• Neurological problems inappropriately
attributed to the epidural i.e. anterior spinal
artery syndrome
• Hypovolemia
The “Hypotensive” Patient with
an Epidural
64 yr. female, 48 kg, with no Hx of CVS problems, had
an esophagectomy for cancer with combined
GA/epidural anesthesia.
Later that evening you are called because the patient’s
BP is 85/50.
Epidural at T5/6 and running hydromorphone 10 µg/ml
in 0.01% bupivacaine at 8 ml/hr
The “Hypotensive” Patient with an
Epidural
Possibilities?
 “Normal” for this patient
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– all is well and confirmed by Hx and absence of
postural changes in BP or HR
– vascular patients may have marked discrepancy
between arms – establish baseline pre-op
Surgical complications
Medical complications
Side-effect of Epidural induced sympathetic block
– decreased venous return and decreased SVR
Combination of any 4 above
Is the Epidural causing the hypotension?
What drugs have been administered epidurally?
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Pure opioids: morphine, hydromorphone,
fentanyl
– sympathetics not blocked directly so look for
another cause
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Demerol
– mild direct sympatholytic effect and some systemic
effects in large doses. Rarely cause of significant
Hypotension. Be careful to R/O other causes.
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Local Anesthetics +/- opioids
– In a euvolemic patient with normal CVS function
hypotension is unlikely if < 8 sensory dermatomes
blocked
Is the Epidural Local Anesthetic
causing the hypotension?
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Intrathecal catheter migration
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Inadvertent overdose
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“Un-masking” of problem with the patient.
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“Sensitive” patient
Is the Epidural Local Anesthetic causing the
hypotension?
Management
 ABCs
– supplemental O2, fluid bolus, elevate legs
– ephedrine 5 mg or phenylephrine 50 µg IV bolus
– Hold the epidural infusion
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Quantify the extent of block
– motor block? Thoracic epidural?, that’s a problem!
– Sensory block (cold, sharp)
• In a euvolemic patient with normal CVS
function hypotension is unlikely if < 8 sensory
dermatomes blocked
Management of Hypotension
Cont’d
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High thoracic epidural blockade may block
the compensatory tachycardia response to
hypovolemia.
– Cardio-accelerator sympathetic nerve fibres arise
from T1 - T4
– sympathetic block may extend several
dermatomes above the sensory blockade
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Correct the underlying cause
Remove bupicacaine and change to epidural
hydromorphone if patient remains
hemodynamically unstable
36 yr. Open Cholecystectomy patient
experiencing difficulty weaning from IV PCA
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Endometriosis, fibromyalgia and chronic low
back pain- has been on Tylenol #3 for several
years- functions well and stable usage of 810/day
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Day 3 post-op Tylenol #3, 2 tabs Q4h started
and IV PCA D/C
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Patient c/o severe pain, not able to go home
36 yr. Open Cholecystectomy patient
experiencing difficulty weaning from IV PCA
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A better way?
Celecoxib 400 mg PO > 2 hours pre-op, after
Naproxen 500 mg PR Q12H to 250 mg PO TID
On day 2, when patient is tolerating diet, review the
24 hour consumption of IV PCA morphine
Multiply the total by 2(for conservative IV to PO
conversion) and divide by 6 to derive the Q4H PO
morphine dose
90 mg IV X 2 = 180 mg, 180 mg/6 = 30 mg PO Q4H
Order the PO morphine straight, plus an additional
half dose for breakthrough pain, prn
Permit 6 hours overlap between IV PCA and PO
Opioid Conversions – Parenteral to Oral
and Equivalents (approx.)
Morphine 10 mg
Morphine 20 mg
Hydromorphone 2 mg Hydro…. 4 mg
Meperidine 75 mg
Meperidine 200 mg
Codeine 120 mg
Codeine 200 mg
Oxycodone (n/a)
Oxycodone 10 mg
Opioid Conversions – Oral to Parenteral
and Equivalents (approx.)
Morphine 40 mg
Hydromorphone 8 mg
Meperidine 300 mg
Codeine 300 mg
Oxycodone 15 mg
Morphine 10 mg
Hydro…. 2 mg
Meperid.. 75 mg
Codeine 120 mg
Oxycodone (n/a)
Conclusion: Key Concepts
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The foundation of all acute pain Rx protocols is
NSAIDS and acetaminophen.
Codeine is a “pro-drug”. Problems may occur with
under or over conversion to morphine
Under utilization of high efficacy PO opioids
Pharmacokinetic + Pharmacodynamic variability
Order opioid dosages rationally, especially with
patient Hx and route of administration in mind
Naloxone can be a dangerous drug, careful titration
is almost always possible
Conclusion
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Think! Foundation of COX-inhibitor
before opioid
– Acetaminophen
– NSAID
– Celecoxib
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COX-2 blockers do not increase
bleeding risk
Conclusions
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Inadequate analgesia despite cyclooxygenase inhibitors and opioids?
– Think “Hyperalgesia”
– Consider an anti-hyperalgesic like
pregabalin
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Codeine is a prodrug
– Extreme variability in extent of conversion
to morphine
ACUTE PAIN MANAGEMENT:
SCIENTIFIC EVIDENCE 2nd Edition June ‘05
Australian and New Zealand College of Anaesthetists
And Faculty of Pain Medicine.
http://www.anzca.edu.au/publications/acutepain.pdf
The above web site has the entire document and is freely
Available to download.