Post on 30-Dec-2015
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Pla
sma c
once
ntr
ati
on
Time
PO: Cmax ~ 60 minutes(oxymorphone ~ 30 minutes )
SQ: Cmax ~ 30 minutes
IV: Cmax ~6 minutes
Pharmacologic administration curvesafter single opioid dose
PRN dosing interval based on time to Cmax:
1 mg hydromorphone iv Q 10 minutes prn
1 mg hydromorphone sq Q 15-30 minutes
Despite these efforts Fred continues to have uncontrolled pain.
How rapidly can you safely escalate his continuous infusion and his prn dose?
PRN dosing interval based on time to Cmax:
1 mg hydromorphone iv Q 10 minutes prn
1 mg hydromorphone sq Q 15-30 minutes
Despite these efforts Fred continues to have uncontrolled pain.
How rapidly can you safely escalate his continuous infusion and his prn dose?
Opioid infusionsDose escalation
Opioid infusionsDose escalation
Opioid infusionsDose escalationOpioid infusionsDose escalation
Adjust bolus dose by up to 100% at least every 30-60 minutes until effective
Adjust infusion rate by up to 100% based on prn need every 12-24 hours
Adjust bolus dose by up to 100% at least every 30-60 minutes until effective
Adjust infusion rate by up to 100% based on prn need every 12-24 hours
The pain crisisThe pain crisis
40 year old man with rectal cancer
S/P abdominoperineal resection
Wound dehiscence
Hospitalized for > 100 days
Daily c/o severe pain
Prescribed 2 mg hydromorphone q 1 hour prn pain
Uncertain how much he had actually been receiving
40 year old man with rectal cancer
S/P abdominoperineal resection
Wound dehiscence
Hospitalized for > 100 days
Daily c/o severe pain
Prescribed 2 mg hydromorphone q 1 hour prn pain
Uncertain how much he had actually been receiving
The pain crisisThe pain crisis
TimeHydromorphon
emg
Response
1300 2 None
1310 4 None
1315 4 None
1330 8 None
1342 8 None
1355 16 None
1415 16 Partial
1430 16 Good/Drowsy
Total 74 mg over 90 minutes
MethadoneMethadone
MethadoneMethadone
Dual effect
Mu-opioid receptor antagonist (analgesia)
NMDA antagonist (prevention/reversal of opioid tolerance)
Variable equianalgesic ratios
Dual effect
Mu-opioid receptor antagonist (analgesia)
NMDA antagonist (prevention/reversal of opioid tolerance)
Variable equianalgesic ratios
MethadoneMethadone
MethadoneMethadone
Dual affect
Mu-opioid receptor antagonist (analgesia)
NMDA antagonist (prevention/reversal of opioid tolerance)
Variable equianalgesic ratios
Variable metabolism
Half life 8 to 190 hours
Plethora of drug-drug interactions
Dual affect
Mu-opioid receptor antagonist (analgesia)
NMDA antagonist (prevention/reversal of opioid tolerance)
Variable equianalgesic ratios
Variable metabolism
Half life 8 to 190 hours
Plethora of drug-drug interactions
MethadoneMethadone
Potent
Effective
Cheap
Complicated
Dangerous
Potent
Effective
Cheap
Complicated
Dangerous
FentanylFentanyl
IV:Transdermal =2:1
Fentanyl IV: Morphine IV roughly 100:1
Transdermal absorption dependent on fat stores
IV:Transdermal =2:1
Fentanyl IV: Morphine IV roughly 100:1
Transdermal absorption dependent on fat stores
Side effectsSide effects
Constipation
Up to 80 % of patients
Requires stimulant laxatives
Does not abate with time
Counseling important
Nausea
Transient
Vestibular mediated
Responds to anticholinergic anti-emetics
Ondansetron is NOT an anticholinergic antiemetic
Educate patients
Constipation
Up to 80 % of patients
Requires stimulant laxatives
Does not abate with time
Counseling important
Nausea
Transient
Vestibular mediated
Responds to anticholinergic anti-emetics
Ondansetron is NOT an anticholinergic antiemetic
Educate patients
Side effectsSide effects
Pruritis
Transient, responds to antihistamines.
Histamine release is pharmacologic property of morphine
Often misinterpreted as allergic reaction
Urinary retention
Rare but potentially serious
Pruritis
Transient, responds to antihistamines.
Histamine release is pharmacologic property of morphine
Often misinterpreted as allergic reaction
Urinary retention
Rare but potentially serious
Side effectsSide effects
Sedation
Especially with initiation or dose increase
Usually resolves
More common with elderly, high dose, polypharmacy
Responds to
Adjuvants/dose reduction
Opioid rotation
Stimulants
Marked sedation requires evaluation
Sedation
Especially with initiation or dose increase
Usually resolves
More common with elderly, high dose, polypharmacy
Responds to
Adjuvants/dose reduction
Opioid rotation
Stimulants
Marked sedation requires evaluation
NeurotoxicityNeurotoxicity
Opioid neurotoxicityOpioid neurotoxicity
55 yo old woman with breast cancer
Pain initially controlled on dilaudid 10 mg/hour
Over the past 10 days pain has worsened despite increase in dilaudid to 50 mg/hr.
Patient is anxious, restless. Complains of pain “all over”
Pain elicited by gently stroking arm
Occasional twitching of chest wall and leg noted.
55 yo old woman with breast cancer
Pain initially controlled on dilaudid 10 mg/hour
Over the past 10 days pain has worsened despite increase in dilaudid to 50 mg/hr.
Patient is anxious, restless. Complains of pain “all over”
Pain elicited by gently stroking arm
Occasional twitching of chest wall and leg noted.
Opioid metabolismOpioid metabolism
Morphine is metabolized in the liver to:
Morphine-6 glucuronide (Active)
Morphine-3 glucuronide (Neuroexictory)
Excreted in the kidney
Morphine-3-glucuronide accumulates in renal failure, high dose and prolonged therapy, oliguria
Morphine is metabolized in the liver to:
Morphine-6 glucuronide (Active)
Morphine-3 glucuronide (Neuroexictory)
Excreted in the kidney
Morphine-3-glucuronide accumulates in renal failure, high dose and prolonged therapy, oliguria
Opioid neurotoxicityOpioid neurotoxicity
Increasing sensitivity to pain (hyperalgesia)
Worsening pain despite rapid opioid escalation
Pain becomes diffuse
Delirium, hallucinations
Allodynia, myoclonus, seizures
Increasing sensitivity to pain (hyperalgesia)
Worsening pain despite rapid opioid escalation
Pain becomes diffuse
Delirium, hallucinations
Allodynia, myoclonus, seizures
Opioid neurotoxicityOpioid neurotoxicity
Risk factors:
High dose
Morphine>hydromorphone>oxycodone, fentanyl, methadone
Renal failure
Oliguria
Can occur at any dose
Risk factors:
High dose
Morphine>hydromorphone>oxycodone, fentanyl, methadone
Renal failure
Oliguria
Can occur at any dose
Opioid neurotoxicityManagement
Opioid neurotoxicityManagement
Prevention, anticipation, early recognition
Assess urine output, magnesium level, electrolyte abnormalities
Hydration if otherwise appropriate
Opioid rotation at 25% equianalgesic dose
Add NMDA antagonist (ketamine or methadone)
Benzodiazepines/phenobarbital based on severity
Prevention, anticipation, early recognition
Assess urine output, magnesium level, electrolyte abnormalities
Hydration if otherwise appropriate
Opioid rotation at 25% equianalgesic dose
Add NMDA antagonist (ketamine or methadone)
Benzodiazepines/phenobarbital based on severity
Opioid refractory pain
Opioid refractory pain
Causes of opioid refractory pain
Causes of opioid refractory pain
Rapid progression cancer
New source of pain
Abscess
Occult fracture
Bladder outlet obstruction
Pain refractory to opioids (Neuropathic pain, skin ulceration)
Opioid related
Malabsorption,
Drug diversion
Toxicity
Fear, existential or spiritual pain
Delirium
Rapid progression cancer
New source of pain
Abscess
Occult fracture
Bladder outlet obstruction
Pain refractory to opioids (Neuropathic pain, skin ulceration)
Opioid related
Malabsorption,
Drug diversion
Toxicity
Fear, existential or spiritual pain
Delirium
Opioid refractory pain-Management
Opioid refractory pain-Management
Opioid rotation or dose escalation
Use of adjuvants, non-opioids
NMDA antagonists (Ketamine and/or methadone)
Address spiritual and psychologic concerns
Non-pharmacologic treatments
Interventional modalities, radiation therapy if appropriate
Consideration of palliative sedation
Opioid rotation or dose escalation
Use of adjuvants, non-opioids
NMDA antagonists (Ketamine and/or methadone)
Address spiritual and psychologic concerns
Non-pharmacologic treatments
Interventional modalities, radiation therapy if appropriate
Consideration of palliative sedation
Barriers to pain reliefBarriers to pain relief
Clinician related
Health care system related
Patient related
Clinician related
Health care system related
Patient related
Patient relatedPatient related
Reluctance to report
“The good patient”
Fear of not receiving chemotherapy
Reluctance to treat
Fears of tolerance
Fear of addiction
Stigma
Meaning of pain
Side effects
“A tradeoff between managing the pain and managing the consequences of managing the pain”
Reluctance to report
“The good patient”
Fear of not receiving chemotherapy
Reluctance to treat
Fears of tolerance
Fear of addiction
Stigma
Meaning of pain
Side effects
“A tradeoff between managing the pain and managing the consequences of managing the pain”
Supporting patient adherence
Supporting patient adherence
Normalize concerns
“Some patients worry about becoming addicted or the drug not working in the future when you need it. Are these of concern to you?”
Non-judgmental questioning:
“It must be really hard to take all these pills. How often, in the last week, have you found that you forget one or two?”
Educate and follow up on likely side effects
Normalize concerns
“Some patients worry about becoming addicted or the drug not working in the future when you need it. Are these of concern to you?”
Non-judgmental questioning:
“It must be really hard to take all these pills. How often, in the last week, have you found that you forget one or two?”
Educate and follow up on likely side effects
“Pain is a multifaceted phenomenon involving not only a tissue damage response but also psychological, social, spiritual and existential domains.
(Nessa Coyle, JPSM, 2004)
“Pain is a multifaceted phenomenon involving not only a tissue damage response but also psychological, social, spiritual and existential domains.
(Nessa Coyle, JPSM, 2004)