KEY CONCEPTS IN ACUTE
PAIN MANAGEMENT - 2
SURGERY RESIDENTS Jan. 5, 2008
John Penning MD FRCPC
Director Acute Pain Service
The Ottawa Hospital
Objectives
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Review the “new” acute pain ladder
When step # 3 on the ladder isn’t working?
– Pronociception, glial activation??
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What is an epidural anyway?
Epidural pitfalls for the surgeon
Review principles discussed by case
presentation
– Opioid tolerance, conversion from IV to PO
– When, how to use naloxone
– Assessing the hypotensive epidural patient
The TOH ATH Analgesic Ladder
Tramacet 2 tabs + HM 2 mg
Tramacet 2 tabs
Acetaminophen 1 tab + Tramacet 1 tab
Acetaminophen 2 tabs
Foundation of NSAID or Coxib
Multi-modal Analgesia Orders

Celecoxib 100 – 200 mg PO Q12H
or

Naproxen 250 – 375 mg PO Q8H
Available OTC as “Aleve” 220 mg
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Acetaminophen 650 mg PO Q4H
Tramacet 1 – 2 tabs PO Q4H prn
Hold 325 mg acetaminophen per Tramacet
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Hydromorphone 1 – 2 mg PO Q4H prn
To supplement Tramacet if required
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:
Hydromorphone 1 – 2 mg PO / SC Q4H prn
Nurse just gave 1 mg S/C 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 6 mg
hydromorphone 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.
Tramacet 1- 2 tabs PO Q4H
Hydromorphone 2 – 3 mg s.c. Q4H
Hydromorphone 0.5 - 1 mg IV Q1H prn
Case Problem:
32 yr. Male with multiple ribs #
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You are at the top of the analgesic
ladder and the patient still has
inadequate control of acute pain.
With more pain is more opioid always
the answer?
NO! Why??
The problem likely is HYPERALGESIA
Scientific American Nov 2009. Pg. 54. Douglas Fields
E = MC2
Hyperalgesia
Pro-nociceptive modulation
Nociceptive
Anti-nociceptive modulation
Stimulus
Analgesia
Pain
Analgesic Drugs that act by
Nociceptive Modulation

Pro-antinociceptive
– Augments inhibitory modulation of
nociception i.e opioids

Anti-pronociceptive
– Inhibits the facilitatory modulation of
nociception i.e. ketamine, gabapentin and
pregabalin
Grande et al. Anesth and Analg Oct 08
NMDA Receptor Antagonists To prevent or reverse “pathological” acute pain

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
0.5:1 with hydromorphone 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 hydromorphone / ketamine
Ketorolac changed to naproxen when
eating. 250 mg PO Q8H
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 hydromorphone.
Daily IV PCA use is 20 mg per day.
Equals about 40 mg per day orally.
Order about 50% as long acting.
9 mg HM Contin Q12H and 2 – 4 mg PO
Q4H prn.
Case Problem:
32 yr. Male with multiple ribs #
Weaning instructions:
As daily “breakthough” hydromorphone
requirements decrease, reduce the
HM Contin dose by 25% increments.
The NSAID or coxib is D/C after the opioids D/C
Acetaminophen is last to be D/C
Analgesic Drugs that act by
Nociceptive Modulation

Pro-antinociceptive
– Augments inhibitory modulation of
nociception i.e opioids

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

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

The Bad
– Mild pain when simple analgesics like
acetaminophen, NSAIDs or low dose opioid or
Tramacet suffice.

The Ugly
– Too large a dose in sleep deprived patient already
in state of “morphine-failure”
Pregabalin dosage

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)
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 a pre-op Anesthesia/APS consult
– The Brief Pain Inventory – “BPI”
Eipe and Penning
2009
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 IV PCA Morphine
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Management of suspected opioid induced
respiratory depression
–
–
–
–
–
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
Opioids
Issue
With parenteral opioids the patient may experience intolerable side
effects before adequate analgesia is attained
Opioids
CONCEPT
Targeted regional
administration of opioid
results in enhancement of
the therapeutic index (ratio
of analgesia/side effects)
Neuraxial Opioids – the good

Intrathecal morphine
– simple technique
– potent analgesia for 12 -16 hrs.
– highly effective for pain in lower abdomen
and lower limbs
Neuraxial Opioids – adverse effects
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Risk of delayed onset of respiratory
depression, peaks at 6 hours
Urinary retention >50% for 16 hours
Pruritus, is not an allergy
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
– Mode of Drug Delivery
– Intermittent bolus vs. continuous infusions
True or False?

Epidural analgesia impairs the
resolution of post-operative ileus i.e. it
“slows down the gut” delaying return of
normal bowel function.

Epidural analgesia necessitates a foley
catheter until the epidural is removed
What about epidurals and the foley
catheter??

Less Urinary Tract Infection by Earlier
Removal of Bladder Catheter in Surgical
Patients Receiving Thoracic Epidural
Analgesia.
Zaouter C, Kaneva P, Carli F (McGill)
Regional Anesthesia and Pain Medicine
Nov-Dec 2009 pp. 542-552.
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

More epidural hematoma risks!!
– Heparin 5000 units s.c. Q8H for
thromboprophyllaxis??
This is full clinical anti-coagulation
for some patients!

Once daily LMWH at thromboprophyllactic
dose is safer.
What about anti-platelet agents?

Plavix
– ASRA guidelines state no neuraxial anesthesia or
epidural catheters implemented until D/C for 7
days –
– Plavix may be started 12 – 24 hour after neuraxial
block or catheter removal
– concensus only, speculative
– Obviously risk is much lower than with
heparin/coumadin since reports are extremely rare
– New agents on horizon??
Epidural Pit-falls for the Surgeon

“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 with epinephrine 2 mcg/ml 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

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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Review of APS meds
– Naproxen 250 mg Q8H
– Pregabalin 50 mg Q8H
– Tramacet 1 – 2 tabs Q4H as needed
– Plus using 20 mg IV HM in last 24 hr.
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Continue above N/P/T plus will likely
require about 40 mg daily HM PO (4 – 6
mg PO Q4H prn)
Plan for transition back to Fam MD
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
Tramadol to be considered as second step in
the acute pain ladder
Naloxone can be a dangerous drug, careful
titration is almost always possible
Conclusions
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Inadequate analgesia despite cyclooxygenase inhibitors and opioids?
– Think “Hyperalgesia”
– Consider an anti-hyperalgesic like
ketamine, pregabalin
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All epidurals are not equivalent
Epidural pitfalls
Useful texts

Free!! From Canadian Pain Society
Managing Pain: The Canadian Healthcare
Professional’s Reference. Edited by Roman Jovey.
2008.
Endorsed by the CPS. Order from Purdue Pharma
on back order – I have ordered for you - March?

Acute Pain Management: A practical guide. 3rd ed. 07
Pamela MacIntyre. Saunders/Elsevier
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.
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.h
tml
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Useful websites on Pain

Pain Institute
http://www.medscape.com/infosite/paininstitute/article5?src=0_0_ad_ldr
Internation Association for the Study of Pain
http://www.iasppain.org//AM/Template.cfm?Section=Home
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