Opioids

Panel Discussion
Problem ?
• 4 out of 10 patients report inadequate postoperative pain
Side Effects
• Immediate postoperative period
• Long-term
The physiology of postoperative pain
• Nociception ?
• Tissue-level mediators such as prostaglandin, serotonin, and
substance P.
• Dorsal spinothalamic pathway to the reticular activating
system, thalamus and finally reach the somatosensory cortex
in the brain.
• Postoperative pain is the patient’s subjective interpretation of
the somatosensory cortex stimulation, and thus is impacted
not only by the nociceptive signal resulting from tissue
disruption and inflammation, but also by complex interactions
among multiple psychological, social, cultural, and physiologic
parameters.
Overview of perioperative pain management
• Manage the patients’ pain expectations AEAP.
• Be multimodal.
• Emphasize patient’s self-efficacy and functional recovery.
Opioids: mechanism of action
• Inhibiting the presynaptic release of substance P
• This leads to inhibition of the ascending transmission of
nociceptive signals through the spinothalamic tract.
• Postsynaptic inhibition >> impeding the pain signal
transmission
Morphine
• Peak 20 minutes after IV administration
• T 1/2 of 3 hours.
• Intramuscular (IM) and subcutaneous administration should
be avoided, why?
• IV administration is very effective in doses of 2 to 3 mg.
• It can be given every 5 minutes until the pain subsides, no SE .
Hydromorphone
• Fast-acting
• 6 times more potent
• Peak within 10 minutes after IV administration.
• T 1/2 2.5 hours.
• IM injection is not recommended.
• IV boluses of 0.2 to 1.0 mg every 2 to 3 hours
Fentanyl
• Synthetic opioid
• 100 times more potent than morphine.
• Peak of within only 4 minutes.
• It rapidly penetrates the blood–brain barrier,
• ICU, MV
– Providers should keep in mind that prolonged administration of fentanyl
– (eg, for >5 days) has been associated with prolonged sedative effect
Opioids: routes of administration
• Oral administration, when feasible, is always preferable.

• Significant variability in terms of absorption (IM, SQ, and TD).
• Undesirable local effects;
– IM morphine injection is ironically painful and
– Subcutaneous morphine may cause a local inflammatory reaction
• The IV route should be used instead as the most reliable mode
of delivery.
Patient-controlled analgesia
• In the awake and capable patient
• To simultaneously avoid delays in pain medication administration
• Avoid respiratory depression
• McNicol and colleagues

• PCA offers superior pain control and increases patient satisfaction.
• The overall opioid consumption was slightly increased without any
difference in the rate of opioid-related adverse events, except for
??, which was more common among the patients receiving PCA.
• Basal opioid infusion should be avoided with PCAs.
• The bolus injections should be followed by a lockout interval of 5 to 10
minutes during which the patients are unable to redose themselves.
• Morphine should be administered in doses of 0.5 to 2.5 mg
(concentration of 1 mg/mL) up to a maximum dose of 30 mg per 4-hour
long periods.
• Hydropmorphone should be given in boluses of 0.05 to 0.40 mg
(concentration of 0.2 mg/mL) up to a maximum dose of 6 mg per 4
hours.
• Fentanyl should be administered in doses of 5 to 20 lg (concentration of
10 lg/mL) up to a maximum dose of 300 lg per 4 hours.
• However, fentanyl should not be the first option for PCA, why?
When to use Fentanyl in PCA?
1. Allergy or
2. Intolerance to morphine or hydromorphone,
3. Renal or
4. Hepatic insufficiency, when the metabolism of morphine and
hydromorphine are impaired, respectively.
Intrathecal and epidural opioids
• Neuraxial analgesia is often more effective than IV opioids in relieving
postoperative pain
• This is why intrathecal or epidural narcotics are being used increasingly,

especially for procedures with predicted significant postoperative pain
(eg, major abdominal and thoracic surgeries) and for opioid-
dependent patients.
• Intrathecal opioids
• Fentanyl (single dose 10–20 lg) is preferred as an intrathecal opioid

• High lipid solubility, fast onset and short duration of action.
• Peak effect in less than 10 mins, the pain relief may last up to 2 hours.
• Morphine (0.1–0.2 mg) is a rather ionized molecule.

• Peak effect to 45 minutes, but the analgesic effects may last up to 24 hrs.
Epidural opioid
• Epidural opioid infusions should be started before the completion of
the procedure.
• Superiority of epidural analgesia in terms of postoperative pain when
compared with systemic opioid administration postoperatively.
• No difference in mortality, postoperative morbidity is improved

– The time to extubation is shorter,
– The incidence of postoperative respiratory failure is decreased,
– The incidence of GI bleeding is decreased,
– The duration of stay in the ICU is shortened significantly
• Most frequently, epidural opioids are given in combination with local
anesthetics, such as bupivacaine 0.125% or ropivacaine 0.2%.
• Superior analgesic results
• Reduces the incidence of narcotic-related adverse effects.
• Similar to the PCA, there is also patient controlled epidural analgesia.

The bad side!
• Misplacement or secondary migration
• Epidural hematomas
• Opioid-related side effects (obese patients with obstructive sleep apnea)
• Delayed respiratory depression
– Morphine several hours after the infusion.
– Patients should be monitored Q1H for the first 12 HRs and then Q2H for the next 12 HRs.
– After the first 24 hours, the patients should be monitored Q3-4H
– Naloxone (opioid antagonist) should be readily available.
• Additionally, given the risk of severe hypotension during the epidural infusion,
vasopressors should be readily available as well
Alternative analgesic modalities
• NSAIDs >> significantly decrease the opioid dose requirements while
maintaining or even augmenting analgesia.
• N-Methyl-D-aspartate receptor antagonists (eg, ketamine), a2-receptor agonists (eg,

clonidine, dexmedetomidine), and anticonvulsant medications (eg, gabapentin) are
additional nonopioid medications that are extremely effective in perioperative pain
management, decrease opioid requirements, and have an overall better safety
profile than opioids
Transversus abdominis plane block
• TAP block used in abdominal wall cases (eg, inguinal hernia repairs), colorectal
surgery, as well as laparoscopic cases.
• In TAP block, local anesthetics are administered between the transversus abdominis
and the internal oblique muscle using US guidance.
• No conclusive absolute indications.
• Better pain control in the first few hours after an operation, but the effect seems to
be fading after 24 hours.
• TAP block does decrease the opioid requirements, but paradoxically it has been
associated with a higher incidence of ??
Adequate perioperative pain assessment
• Pain is classically assessed using visual analog or verbal scales from 0 to
10, but we recommend that surgeons assess the patients’ functional
pain, that is, how their pain is impairing their daily functions (or not).
• The amount of tissue disruption is inherently different for an emergent

colectomy as compared with an elective inguinal hernia surgery, and
thus procedure-specific pathways and guidelines for pain control should
be sought and implemented, when appropriate
Consideration for alternatives to opioids
• Opioids should not be the first or only resort to address perioperative pain.
• Nonopioid pain relievers such as ketorolac, acetaminophen, gabapentin, or

clonidine and locoregional anesthesia such as peripheral nerve blocks or
topical anesthetic agents should be used systematically, when possible.
• Surgeons should be aware that baseline or perioperative psychological

factors could be contributing to the patients’ perception of pain such as
stress, anxiety, depression, or sleep deprivation.
Risk assessment for opioid misuse
• When evaluating a patient preoperatively, the surgeons should refer
patients with signs suggestive of substance abuse history to substance
abuse specialists when appropriate.
Limitation of the dose and duration of opioid prescribing
• Only the necessary dose and the necessary duration of narcotics should
be given and/or prescribed.
• In Massachusetts, this should be limited to a 7-day supply, unless

appropriately justified.
Management of patient expectations
• Some experts suggest that less opioid use does not necessarily lead to
worse pain or worse patient satisfaction.
• Counseling
(1) the goal of pain management is not its complete resolution, but its
improvement to tolerable levels that allow return to daily activities,
(2) opioids have serious side effects, including a risk of addiction, and
(3)Medications alternative to opioids are effective.
• Upon discharge from the hospital, safe methods to discard any extra
pills should be clearly discussed with the patient.
• Which surgeries need more analgesia?
• Why to use morphine for most post-op analgesia?
• Why not PO or IV?
• PRN or ATC?
• The best alternative for opioids?
• Single oral agents?
• Good (low) NNTs were obtained with ibuprofen 200 mg plus paracetamol
(acetaminophen) 500 mg (NNT compared with placebo 1.6; 95%
confidence interval 1.5 to 1.8), ibuprofen fast acting 200 mg (2.1; 1.9 to
2.3); ibuprofen 200 mg plus caffeine 100 mg (2.1; 1.9 to 3.1), diclofenac
potassium 50 mg (2.1; 1.9 to 2.5), and etoricoxib 120 mg (1.8; 1.7 to 2.0).
• There is a wealth of reliable evidence on the analgesic efficacy of single

dose oral analgesics.
• Fast acting formulations and fixed dose combinations of analgesics can
produce good and often long‐lasting analgesia at relatively low doses.
• For ibuprofen 200 mg + caffeine 100 mg particularly, the low
NNT value is among the lowest (best) values for analgesics in
this pain model.
• The combination is not commonly available, but can be

probably be achieved by taking a single 200 mg ibuprofen
tablet with a cup of modestly strong coffee or caffeine tablets.
• A single oral dose of dexketoprofen 25 mg plus tramadol 75
mg provided good levels of pain relief with long duration of
action to more people than placebo or the same dose of
dexketoprofen or tramadol alone.
• The magnitude of the effect was similar to other good

analgesics. Adverse event rates were low.
• There was limited evidence available to draw any conclusions
about the efficacy of PRN versus ATC analgesic administration
for the management of postoperative pain in children.

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Panel Discussion

• Oral administration, when feasible, is always preferable.

• McNicol and colleagues

• This is why intrathecal or epidural narcotics are being used increasingly,

• Fentanyl (single dose 10–20 lg) is preferred as an intrathecal opioid

• Morphine (0.1–0.2 mg) is a rather ionized molecule.

• No difference in mortality, postoperative morbidity is improved

• Similar to the PCA, there is also patient controlled epidural analgesia.

• N-Methyl-D-aspartate receptor antagonists (eg, ketamine), a2-receptor agonists (eg,

• The amount of tissue disruption is inherently different for an emergent

• Nonopioid pain relievers such as ketorolac, acetaminophen, gabapentin, or

• Surgeons should be aware that baseline or perioperative psychological

• In Massachusetts, this should be limited to a 7-day supply, unless

• There is a wealth of reliable evidence on the analgesic efficacy of single

• The combination is not commonly available, but can be

• The magnitude of the effect was similar to other good

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