Transcript Pharmacodynamic Profile of Enadoline, A Selective Kappa (k

Treating Acute Pain in Patients
Maintained on Buprenorphine
and Methadone
AOAAM, October 26, 2010
Karen Lea Sees, DO, FAOAAM
Pain Treatment
in Patients with or without an Addiction
• Is the distinction important?
• Current, recent or remote addiction?
• Drug of choice?
• Acute versus chronic pain?
Treating patients on opioid agonist therapy (OAT) who
are experiencing acute pain is complicated.
There is some research that can inform this discussion,
and there are also clinical recommendations that can
help guide treatment.
Acute Pain Treatment in Patients on OAT
• These patients suffer thrice:
- from the painful disease
- from the addiction, which makes pain management
difficult
- from the health care provider’s ignorance
Acute Pain Treatment in Patients on OAT
• Is it appropriate to bar the prescribing of controlled
substances to anyone?
• Is it just to deny a patient with an addiction pain
medication simply because of their addiction status?
Acute Pain Treatment in Patients on OAT
• Definitions:
-
Physical dependence: normal physiologic adaptation
defined as the development of withdrawal or abstinence
syndrome with abrupt dose reduction or administration of
an antagonist
-
Therapeutic dependence: Patients with adequate pain
relief may demonstrate drug-seeking behaviors because
they fear not only the reemergence of pain but perhaps
also the emergence of withdrawal symptoms
-
Substance dependence: maladaptive behaviors, including
loss of control
Acute Pain Treatment in Patients on OAT
• Definitions:
-
Cross-tolerance: Normal neurobiological event of
tolerance to effects of medication within the same class
-
Opioid-induced hyperalgesia: A neuroplastic change in
pain perception resulting in an increase in pain sensitivity
to painful stimuli, thereby decreasing the analgesic
effects of opioids
-
Drug-seeking behaviors: directed or concerted efforts to
obtain opioid medication
-
Pseudoaddiction: behaviors such as drug-seeking that are
secondary to inadequate pain control and not to addiction
Acute Pain Treatment in Patients on OAT
Must consider:
• Potential for therapeutic efficacy
• Risk of adverse consequences, including relapse
• Possibility of iatrogenic addiction
• High tolerance to medications
• Low pain threshold
Acute Pain Treatment in Patients on OAT
• Four misconceptions:
- Maintenance OAT provides analgesia
- Use of opioids for pain treatment may result in
relapse
- Opioids for pain plus OAT will lead to respiratory
depression
- Pain complaint may be manipulation
Acute Pain Treatment in Patients on OAT
• Four misconceptions:
- Maintenance OAT provides analgesia
- Use of opioids for pain treatment may result in
relapse
- Opioids for pain plus OAT will lead to respiratory
depression
- Pain complaint may be manipulation
Acute Pain Treatment in Patients on OAT
- Suppression of withdrawal/abstinence syndrome is
24-48 hours
- Analgesic duration is 4-8 hours
- Because of cross-tolerance analgesia may not
last as long as expected
- Dose may need to be higher and more frequent
than expected to achieve adequate pain control
Acute Pain Treatment in Patients on OAT
• Four misconceptions:
- Maintenance OAT provides analgesia
- Use of opioids for pain treatment may result in
relapse
- Opioids for pain plus OAT will lead to respiratory
depression
- Pain complaint may be manipulation
Acute Pain Treatment in Patients on OAT
- Small retrospective study found no difference in
relapse in MMT patients who received opioids
after surgery
Kantor et al., 1980
- No relapse in MMT patients who received opioids
to treat chronic cancer pain
Manfredi et al., 2001
Acute Pain Treatment in Patients on OAT
- Study comparing addicts with AIDS to cancer
patients and their response to undertreatment
- Aberrant behavior was set in motion by undertreatment of pain
Passik et al. 2002.
- MMT patients claim pain plays a substantial role in
their initiating and continuing drug use
Karasz et al., 2004
Acute Pain Treatment in Patients on OAT
• Four misconceptions:
- Maintenance OAT provides analgesia
- Use of opioids for pain treatment may result in
relapse
- Opioids for pain plus OAT will lead to respiratory
depression
- Pain complaint may be manipulation
Acute Pain Treatment in Patients on OAT
- Risk is theoretical, but never been clinically or
empirically demonstrated
Alford et al., 2006
Acute Pain Treatment in Patients on OAT
• Four misconceptions:
- Maintenance OAT provides analgesia
- Use of opioids for pain treatment may result in
relapse
- Opioids for pain plus OAT will lead to respiratory
depression
- Pain complaint may be manipulation
Acute Pain Treatment in Patients on OAT
- Concerns are substantial, difficult to quantify, and
emotion laden
- Pain is subjective
- Acute pain should have subjective findings
- OAT dose will not treat the pain, but should block
most of the euphoria effects from supplemental
opioids, thus theoretically reducing the likelihood
of abuse
Acute Pain Treatment in Patients on OAT
- Patients may be demanding:
- Distrust of medical community
- Concern about stigma
- Fear of undertreated pain
- Fear that OAT may be altered or discontinued
- May be drug-seeking for good reason
(pseudoaddiction)
Acute Pain Treatment in Patients on OAT
• Use adjunctive modalities and medications
• Avoid the patient’s drug of choice
• Use medication with lower street value
• Avoid self administration, if possible
Acute Pain Treatment in Patients on OAT
• Explain potential for relapse
• Explain the rationale for the medication
• Educate the patient and the support system
• Encourage family/support system involvement
• Frequent follow-ups
• Consultations
Acute Pain Treatment in Patients on OAT
• Address addiction
• Use non-medication approaches, if effective
• Use non-opioid analgesics, if effective
• Provide effective opioid doses, if needed
• Use ATC not PRN dosing
• Treat associated symptoms, if indicated
• Address addiction
Acute Pain Treatment in Patients on OAT
Symptomatic pain therapies:
• Pharmacological
• Rehabilitative
• Psychological
• Anesthesiologic
• Surgical
• Neurostimulatory
• Lifestyle changes
Acute Pain Treatment in Patients on OAT
• Post-operatively
• Acute medical conditions
• Acute trauma
Acute Pain Treatment in Patients on OAT
• Must satisfy baseline opioid requirements before
treating pain
• The usual maintenance dose (e.g., methadone or
buprenorphine) will not control the pain
• The usual maintenance dose needs to be
supplemented with appropriate medication(s) for
pain control
• May need slightly higher amounts for slightly
longer periods of time
Pain Control for OAT Patients
• Mixed agonist and antagonist opioid analgesics
such as pentazocine, nalbuphine, and butorphanol,
must be avoided because they probably will
displace the OAT from the mu-receptor, thus
precipitating withdrawal
• Combination products are often problematic
because of the amount of acetaminophen
Acute Pain in Patients on Buprenorphine
Very little systematic research to guide
recommendations
Guidelines based on available literature, pharmacologic
principles, and published recommendations
Because of the highly variable rates of buprenorphine
dissociation from the mu-receptor, naloxone should be
available and level of consciousness and respiration
should be frequently monitored
Acute Pain in Patients on Buprenorphine
Two general clinical situations for acute pain
Pre-planned (an elective procedure)
Unplanned (an accident)
Buprenorphine
• Buprenorphine has a slow weaning effect throughout
12 to 24 hours, may be up to 72 due to high affinity
for but only partial activation of the mu-opioid
receptors that prevent displacement and further
activation by full opioid agonists
Acute Pain in Patients on Buprenorphine
If planned, can strategize steps to be taken beforehand
Anticipated level and duration of pain
Setting in which pain management will occur
Timing of buprenorphine dosing relative to dosing of pain
medication (especially if using a full agonist opioid for
pain control)
Supports to help the patient with the pain
Discussion with patient regarding risks associated with
use of opioids and nonopioids for pain management
Acute Pain in Patients on Buprenorphine
If planned
Stop daily dose of buprenorphine 1 to 2 days before the
scheduled procedure
Convert to pure mu agonist
Acute Pain in Patient on Buprenorphine
If unplanned
While the patient is generally not prepared for how
to handle pain, the clinician can be prepared
Consider in advance how unplanned acute pain will be
managed for patients maintained on buprenorphine
(e.g., identify preferred types of nonopioid and
opioid medications)
Acute Pain in Patient on Buprenorphine
Treatment of unplanned acute pain
Maintenance dose of buprenorphine will not provide
pain relief – other treatments will be needed
First consider use of nonopioid medications and/or
regional analgesia added to buprenorphine
Acute Pain in Patients on Buprenorphine
Treatment of unplanned acute pain (continued)
If nonopioids are not effective, use opioids; options
include:
Divide the daily dose of buprenorphine and
administer it every 6 to 8 hours
Add supplemental doses of buprenorphine to
maintenance buprenorphine dose (a theoretical
option, but no studies to date on this and may
find ceiling effect limits amount of analgesia
achieved)
Acute Pain in Patients on Buprenorphine
Treatment of unplanned acute pain (continued)
If short acting opioid are needed:
- Consider switching from buprenorphine to a full
agonist opioid (e.g., methadone)
- Combining buprenorphine with a short acting
opioid could produce a precipitated withdrawal
syndrome
Acute Pain in Patients on Buprenorphine
Treatment of unplanned acute pain (continued)
If you need to use a short acting opioid and you decide
to not switch from buprenorphine to a full agonist
opioid (e.g., methadone):
- Time buprenorphine administration to occur well
after expected peak effect of short acting opioid
- Note that higher doses of the short acting opioid
may be needed to achieve pain relief (given
buprenorphine’s high affinity for the mu opioid
receptor)
Acute Pain in Patient on Buprenorphine
Treatment of unplanned acute pain (continued)
If temporarily switching a patient from
buprenorphine to a full agonist opioid, stop
buprenorphine and:
- Treat pain with full agonist opioid (short or long
acting, may need more due to tolerance)
- Once pain gone, stop full agonist opioid and allow
mild withdrawal
- Restart buprenorphine
Acute Pain in Patient on Buprenorphine
Treatment of unplanned acute pain (continued)
If hospitalized the maintenance buprenorphine dose
can be converted to 30 to 40 mg/d of methadone
Injectable Buprenorphine for the
Treatment of Pain
Injectable form of buprenorphine is approved and
available for treatment of pain, but sublingual form is
not FDA approved for this indication
Injectable buprenorphine is an effective analgesic;
typical dose is 0.3 mg (IV/IM) given every 4-6 hours
Rapid onset of effects
Preclinical studies have shown bell-shaped dose
response curve for analgesia
Buprenorphine Overdose
• Administration of 2 mg naloxone will have no effect
on mild respiratory depression (onset 15 minutes,
maximum effect at 45 minutes and lasts up to 6
hours)
• Higher doses of 5 or 10 mg may have some effect of
respiratory depression but little effect on mental
status changes
Buprenorphine Overdose
• High-dose naloxone and/or rapid infused naloxone
may cause catecholamine release resulting in
pulmonary edema and cardiac dysrrhythmias
• AND an acute withdrawal syndrome
Dorp et al., informahealthcare.com, 2007
Acute Pain in Patient on Methadone
Treatment is the same for planned or unplanned acute pain
Anticipated level and duration of pain
Setting in which pain management will occur
Supports to help the patient with the pain
Discussion with patient regarding risks associated with
use of opioids and nonopioids for pain management
Acute Pain in Patient on Methadone
Two approaches to opioids:
Primary:
Continued maintenance methadone dose
Supplement with additional pure mu-agonists (e.g.,
morphine or hydromorphone)
Wean supplemental opioids as pain resolves and continue
maintenance dose
Alternate:
Divide and supplement the methadone maintenance dose
for q 6-8 dosing regimen (analgesic duration 4-8 hours)
Acute Pain in Patients on Methadone
If patient is NPO then use IM or SQ in half to 2/3 the
maintenance dose divided into 2 to 4 equal doses
Pain Treatment
in Patients with an Addiction
• Physicians must learn communication skills for
discussing opioid misuse and abuse with patients
• Because these discussions are potentially
uncomfortable, they are often delayed, addressed
poorly or never addressed at all
Aberrant Drug Related Behaviors Less Predictive of an Addiction
• Aggressively complaining of the need for more drug
• Drug hoarding during periods of reduced pain
• Requesting specific drugs
• Openly acquiring similar drugs from other medical
sources
• Unsanctioned dose escalation or other non-compliance
on one or two occasions
Aberrant Drug Related Behaviors Less Predictive of an Addiction
• Unapproved use of drug to treat another symptom
• Reporting psychic effects not intended by the
clinician
• Resistance to change in therapy associated with
“tolerable” side effects with expression of anxiety
related to return of severe pain
Aberrant Drug Related Behaviors More Predictive of an Addiction
• Selling prescription drugs
• Prescription forgery
• Stealing or “borrowing” drugs
• Obtaining prescription drugs form non-medical
sources
• Concurrent abuse of alcohol or illicit drugs
• Multiple dose escalations or other non-compliance with
therapy
Aberrant Drug Related Behaviors More Predictive of an Addiction
• Episodes of prescription “loss”
• Prescriptions from other clinicians/EDs without
seeking primary prescriber
• Deterioration in function that appears to be related
to drug use
• Resistance to change in therapy despite significant
side effects from the drug
Differential Diagnoses of
Aberrant Drug Related Behaviors
• Addiction
• Pseudoaddiction
• Other psychiatric disorder
• Encephalopathy
• Family disturbance
• Criminal intent
• Exacerbation of pain syndrome
• Side effect(s) of opioid
Differential Diagnosis of Functional Downturn
• Syndrome of opioid abuse/dependence
• Other substance use disorder
• Other psychiatric disorder
• Exacerbation of pain syndrome
• Other medical problem
• Side effect of opioid
Controlling Aberrant Drug-Related Behaviors
• Frequent office visits
• Written consents
• Small amounts of medication
• Pill counts
• One pharmacy
• Exclude replacement/early prescriptions
• Require police report for lost/stolen medications
• Random urine testing
• Consultations
Summary
• Substance abuse issues are complex during pain management
and they defy simple solutions
• Use of opioids for treatment of acute pain is often
appropriate, and can be safe and effective
• Important to recognize appropriate patients for opioids
• Design and communicate treatment plan and consent
• Special attention is needed when treating opioid maintained
patient:
- Do not leave them in pain, if relief is possible
- Monitor more closely
- Caution in patients maintained on buprenorphine