Transcript Using Opioids for Pain

Using Opioids for Pain
A continuous infusion of
knowledge with intermittent doses
of pain
Nicole L. Artz, MD
You are the intern on call. You admit a 70
year old woman with severe pain from a
compression fracture of her lumbar spine.
 She has not had adequate relief from tylenol
or ibuprofen at home. Her son has
accompanied her to the hospital and
mentions that he is a malpractice attorney.
 Recognizing that pain is the 5th vital sign, you
vow to control her pain and, since the
Duragesic drug rep bought your lunch
yesterday, you apply a 25 mcg fentanyl patch
immediately.

You are busy with other patients and
don’t have a chance to check on her
again for around 5 hours.
 You find her moaning in pain.
 You start a dilaudid PCA with a basal
infusion rate of 1.0 mg/hr and rescue
doses of 0.5 mg q 15 minutes. You ask
the nurse to call you if she is still in pain
once the PCA is started.
 You get busy again with more
admissions but assume that her pain
must be better controlled because you
haven’t heard anything from the nurses.

Just at that moment you hear a “Dr.
Cart” called to her room.
 On arriving you are horrified to find that
she is unarousable, hypotensive, and
only breathing 4 times/minute.

What
happened?
Outline
Misperceptions about Addiction
 Opioids to Avoid
 General Principles
 PCA’s
 Special Populations
 Methadone
 Practice Cases

Tolerance
Diminished drug effect over time due to
ongoing drug exposure- i.e. takes
higher dose to get relief.
 Desireable in the case of side effects.
 * Which side effect do patients NOT
develop tolerance to?
 Tolerance does NOT cause addiction.

Physical Dependence
Physiologic changes expected to occur
with ongoing exposure to opioids.
 Similar changes occur w/ other
medications (beta blockers, antidepressants, alpha-2 agonists….).
 Abrupt opioid withdrawal results in
withdrawal syndrome.

Physical Dependence Cont.

Signs/symptoms of opioid withdrawal:
– Tachycardia, nausea, vomiting, diarrhea,
rhinorrhea, lacrimation, yawning, anxiety.

Avoid by tapering dose by 50% every 2-3
days.

Does NOT imply or cause addiction.
Pseudoaddiction

Aberrant behaviors occurring as a result of
under-treated pain.
– “clock-watching”
– Aggressive complaining
– Requesting specific drugs
– Unsanctioned dose escalation

*Behaviors decrease or resolve with
improved pain control.
Addiction
Psychological dependence on a drug.
 Fundamental features include:

– Loss of control
– Compulsive use
– Use despite harm
Addiction, Cont.

Behaviors more likely to be related to
addiction:
– Prescription forgery
– Stealing or “borrowing” drugs
– Multiple episodes of prescription “loss”
– Concurrent abuse of related illicit drugs
– Selling prescription drugs
Are there opioids to avoid?

Demerol
Poorly absorbed orally, short half-life (3
hrs)
 Normeperidine
–
–
–
–

non-analgesic metabolite
long half-life
renally excreted
Toxic-- CNS excitation (tremors, anxiety,
dysphoria, myoclonus, seizures) with
accumulation
Frequent dosing required leads to
inevitable accumulation of metabolite,
esp. in setting of renal insufficiency.
Indications for Demerol:

If patient has a history of 1 or more of the following:
– Unmanageable adverse reactions to other 1st line
opioids.
– Tx failure to other 1st line opioids given in adequate
doses.
– Prevention/tx of drug/ blood product induced rigors
– Single injection conscious sedation for procedures

Should not be used >48 hrs. or >600 mg/day
 Propoxyphene (Darvon, Darvocet)

Not any more effective than
tylenol or aspirin.

Toxic metabolite with a half-life of
30-36 hrs(!) also renally excreted–
repeat dosing may lead to
accumulation of metabolite esp in
setting of renal insuff– results in
seizures, cardiac toxicity, pulmonary
edema…general badness.
Which drug should I start with?
Morphine is the gold standard but can use
any opioid- just make sure to dose
correctly.
 Keep cost in mind.
 In general, reserve fentanyl patches for
patients who are unable to swallow pills or
are on a stable dose of opioid since it is
difficult to titrate and is very expensive.

What about patients with hepatic
or renal disease?


Opioids 90-95% renally cleared
Renal Disease

Less of an issue w/ liver disease but with severe
hepatic dysfunction increase the dosing interval
or decrease the dose.
– Morphine - 2 metabolites: M6G is active and has a
longer half-life than morphine. As a result–
decrease the dose, widen the interval, use PRN
or not at all.
– Safer to use dilaudid, methadone, fentanyl but still
consider starting w/ half the usual dose and/or
increasing the interval.
What if the patient has a
morphine allergy?
Most “allergies” are actually
unexpected adverse effects.
 If evidence of a true allergy- hives,
bronchospasm, anaphylaxis or can’t
be sure, can safely use:
– Fentanyl
– Methadone
– ?Dilaudid

What is the maximum dose?

There is no “ceiling effect” with the pure
opioids (exception of codeine). Keep
titrating until the pain is controlled or the
dose is limited by adverse effects.
How fast can I titrate?
Great question!
 Some lack of consensus–
 Short acting oral opioids can be titrated
quickly- dose by dose.
 Sustained release oral opioids can be
dose-escalated every 24-72 hrs.
 Transdermal fentanyl should not be
dose escalated more often than every
72 hrs.
 Methadone should not be titrated more
often than every 5-7 days.

How much should I increase the
dose?
Mild Pain- increase by 25%
 Moderate Pain- increase by 50%
 Severe Pain- increase by 100%
 Example- Pt receiving 5 mg morphine
IV q3hrs with severe pain can go up to
10 mg IV q 3 hrs.
 Don’t go from 5 mg morphine q 3 hrs
to 6 mg morphine q 3hrs.

How should I treat
breakthrough pain?
Offer an immediate release opioid.
 Give 10-15% of the 24 hour dose.
 Peak analgesic effect correlates with the
peak plasma concentration.
 Extra breakthrough doses:

– Q 1-2 hrs for po route
– Q 30 minutes for SC or IM route
– Q 15 minutes for IV route.
How do I convert from one
opioid to another?
Everyone needs an equianalgesic chart.
 Used to convert opioids and also routes
(IV – PO).
 Provides a guide– in general, start a new
opioid at 50-75% of the calculated
equianalgesic dose to allow for incomplete
cross-tolerance between different opioids.

PCA’s….
Loading dose
 Basal rate
 Demand dose
 Lockout

PCA’s- Basal Rate
Do not use a basal rate in patients
who are opioid naiive. This
undermines the safety mechanism of the
PCA.
 If not opioid naiive, calculate the 24hr
dose of currently used opioids and convert
to an equianalgesic basal rate.

PCA’s Bolus Dose
May use a loading dose when initiating a
continuous infusion or when increasing the
basal rate.
 Rescue dose usually 50-150% of basal
rate.

Example– Pt on morphine basal rate 2mg/hr.
Could set rescue (demand dose) anywhere
from 1-3 mg available Q15 minutes.
PCA’s cont.
Reassess
frequently!!!
May adjust the bolus dose every 30
minutes until desired effect.
 May adjust the basal rate every 8 hrs.
 Consider the number of bolus doses as
guide.
 Never increase the basal rate more than
100% at any one time.

Loading Dose Range
(Opioid naïve pt)
<65/70 kg
Morphine
Dilaudid
Demerol
1-3 mg
0.2-0.6 mg
10-30 mg
>65 y/o
0.5-2 mg
0.1-0.4 mg
5-20 mg
7-12/<50 kg
(dose per kg)
0.01-0.03 mg
0.002-0.004 mg
0.1-0.2 mg
Size of the loading dose is influenced by:
Age
Physical status
Lean body weight
Opioid tolerance
>12/>50 kg
0.5-2 mg
0.1-0.4mg
5-20 mg
Maintenance Dose Range
<65/70 kg
>65 y/o
7-12/<50 kg
(dose per kg)
0.01-0.03 mg
>12/>50 kg
Morphine
0.5-1.5 mg
0.5-1 mg
Dilaudid
0.1-0.3 mg
0.1-0.2 mg
0.002-0.006 mg
0.1-0.2 mg
Demerol
5-15 mg
5-10 mg
0.1-0.2 mg
5-10 mg
0.5-1 mg
Sedation Scale
0 = Awake and alert
1 = Occasionally drowsy, but easy to arouse - - needs
verbal stimulus only to become awake and stay alert.
2 = Frequently drowsy, arousable but may close eyes
during conversation - - needs verbal & brief light tactile
stimulus to become awake and stay alert.
3 = Somnolent, difficult to arouse - - needs repeated
verbal & tactile stimulus to rouse; minimal to no response to
stimulation.
PCA’s

Do not start a PCA and then disappear for
24 hrs.
Reassess
frequently!
Trust the patient’s report
of pain.
Methadone
Great drug for use in chronic pain
 The LEAST expensive of all opioids (by
far)
 Safe even with ESRD
 Dosed q 6-12 hrs
 Extremely long and variable half-life (up
to 190 hours!)
 Do not titrate more often than once
every 5-7 days

Methadone Cont…
Racemic mix: one stereoisomer is a mu
opioid receptor agonist, the other a NMDA
receptor antagonist.
 NMDA mechanism results in lower opioid
tolerance, and may be the reason for
increased efficacy with neuropathic pain.
 Methadone behaves as a much more
potent opioid the higher the dose of the

prior opioid.
Important to use MEDD table
MS daily dose
Morphine/Methadone
 < 30
 30-99
 100-299
 300-499
 500-999
 >1000

2:1
4:1
8:1
12:1
15:1
20:1
Let’s Practice…
Case 1

55 y/o woman with ovarian cancer on MS
Contin 60 mg po q 12 at home. She
needs hospitalization for nausea/vomiting
following chemo. You are the intern on
call. Calculate the equivalent IV dose.

60 mg po q 12= 120 mg/d

120 mg po MSO4/d = 30 mg po MSO4
X mg IV MSO4/d
10 mg IV MSO4
Case Cont…
X
= 40 mg IV MSO4/d = 1.5-2.0
mg/hr
 Demand
dose?
 Loading
dose?
Case Cont..
The PCA machine will not be available for
a few hours.
 You give her Phenergan for nausea. How
much IV morphine will you give her as a
one time dose?
 15 minutes later her pain score has
decreased from 10 to 8. Should you
redose? How much should you give?

Case 2

45 year old woman with breast cancer
metastatic to bone. She is comfortable on a
continuous infusion of morphine at 6 mg/hr. You
need to change her to oral medication before
discharge home.

6 mg/hr X 24 hrs = 144 mg/day IV morphine
144 mg/d IV MSO4 = 10 mg IV MSO4
X mg/d po MSO4
30 mg po MSO4
Case Cont…

X = 432 mg morphine po/day
– Sig: 200 mg extended release morphine po bid

Prescribe a breakthrough dose of 10-15%
of the total daily dose.
– Sig: 45-60 mg immediate-release mophine po
q 1 hr prn.
Case 3

45 y/o man with chronic pancreatitis, transferred
from an OSH. He has been receiving 100 mg
Demerol IV q 3 hrs for pain and is now
tolerating po with adequate pain control. You
want to calculate an equivalent dose of a
fentanyl patch.

100 mg X 8 = 800 mg IV Demerol/24 hrs
800 mg IV Demerol/d =
X mg po Morphine/d
100 mg IV Demerol
30 mg po Morphine
Case 3 Cont…

X = 240 mg morphine/24 hrs
 Reduce dose by 25-50% to account for incomplete
cross-tolerance.
120-180 mg morphine/day

Use 2:1 rule: (50 mg morphine/d = 25mcg fentanyl
patch
– 150 mg po morphine = 75mcg duragesic patch

Don’t forget a breakthrough dose.
– 10% of 150 mg morphine= 15 mg po IR MSO4 q 2
hrs prn pain.
Case 4

45 y/o man with chronic pancreatitis, transferred
from an osh. He has been receiving 200 mg
Demerol IV q 2 hrs for pain. You want to put
him on a Dilaudid PCA.

75 mg X 12 = 2400 mg IV Demerol/24 hrs
2400 mg IV Dem./24hrs = 100 mg IV Demerol
X mg IV Dilaud./24hrs
1.5 mg IV Dilaudid
Case 4 Cont…
X = 36 mg IV Dilaudid/day
 Adjust for incomplete cross-tolerance
0.50(36)= 18 mg/day
 Basal rate = 0.75 mg/hr
 Order a rescue dose:
0.75 mg available Q 10 minutes on
demand

Case 4 Cont…
2 hours after the PCA is started you
reassess the patient and find that he is
hitting his demand button 3 times/hour
and is still moderately uncomfortable.
 What should you do?
 How much should you increase the
demand dose?
 How could we have avoided this
situation?

Back to our Patient

What went wrong?
– The fentanyl patch is a poor choice in an opioid
naiive patient. (Equivalent to approx 50 mg
morphine/day!)
– No effect for 6-12 hrs- no wonder she was still in
the same amount of pain 5 hrs later! *Remember
to always prescribe IR breakthrough pain
medication with a fentanyl patch.
– Never use two long-acting (basal) opioids at once.
Fentanyl patch likely started to work at the same
time she was started on the PCA with basal rate.
Use great caution when starting a basal
rate in an opioid naiive patient.
 Always underestimate opioid needs in
the elderly and titrate up as needed.

References:
National Comprehensive Cancer Network:
Practice Guidelines in Oncology- v.2.2005
 Principles of Analgesic Use in the
Treatment of Acute Pain and Cancer Pain,
American Pain Society, Fifth edition, 2003.
 Education for Physicians on End-of-Life
Care (EPEC), Pain Management Module,
RWJF, 1999.

Resources
Hopkins Opioid Program- amazing, free
downloadable program for your palm pilot
that automatically does the calculations
for you.
 Fast Facts, National Residency End-ofLife Curriculum Project
Download at www.eperc.mcw.edu
