Before starting opioids, remember the following please:

• Non-opioids should be tried first.

• All opioids can cause respiratory depression. Delay using opioids in those with decreased levels of consciousness or RR < 10.

• Morphine and hydromorphone induce histamine release causing itching, hypotension, and bronchospasm. Hypotension particularly can be profound with some opioids! It’s better to delay administering opioids until BP is more stable (See Fentanyl & Remifentanyl below).

• Bradycardia is a side effect of opioids, use extreme precautions in patients with HR <50 and avoid it if HR < 40.

• Use extra precautions when using opioids in elderly patients, morbidly obese patients, and patients with OSA (Obstructive sleep apnea) and OHS (Obesity hypoventilation syndrome).

• Telemetry and continuous pulse oximetry monitorings should be performed in all patients receiving opioids in the hospital, this is paramount in elderly patients, OSA, and OHS patients.

Mepiridine & Codeine:

• Meperidine is associated with significant neurotoxicity and I don’t see why should we use it anymore.
• Codeine has low potency and shouldn’t be used for analgesia, you still can use it for some cases of severe dry cough.

Fentanyl and remifentanil:

• They are very potent analgesics, each 1 mg of fentanyl or remifentanil is equivalent to 100 mg of IV morphine, that’s why they are dosed in mcg, not mg.
• They are not associated with histamine release which means less hypotensive effect making them appropriate for patients with hemodynamic instability.

• They are safe in advanced hepatic and renal impairment

• They have a quick onset followed by a quick offset, with an onset of action within three minutes and a duration of action of 30-60 minutes for fentanyl and 5-10 minutes for remifentanil, the ultra-short action of remifentanil makes it only appropriate for continuous infusion only! Fentanyl, on the other hand, is preferably used as a continuous infusion but can be given on an as-needed basis every 30-60 minutes, please don’t order fentanyl PRN every 4-6 hours.

• The starting dose for fentanyl is 1-2 mcg/kg which typically ranges between 25-100 mcg and should be ordered like this:
  • Fentanyl 25 mcg IV Q60 minutes PRN severe pain

• For remifentanil, I recommend you look it up as it’s given as adrip with or without a loading dose.

• All these characteristics make fentanyl and remifentanil ideal for critically ill patients, remifentanil can be very helpful when frequent neuro checks are required given its ultra-short effect, its effect wears off in minutes.
• Fentanyl patch should be used in chronic pain only, not acute pain management similar to extended-release opioids.

Hydromorphone:

• It comes in oral & IV preparation.

• More potent than morphine, each 1 mg of IV hydromorphone is equivalent to 7 mg of IV morphine, while 1 mg of oral hydromorphone is equivalent to 4 mg of oral morphine.

• It can be given every 2-4-6 hours or as part of PCA.

• Safe in advanced renal and hepatic impairment although dose adjustment may be required in advanced renal impairment.

• Associated with Histamine release leading to itching, hypotension, and possibly bronchospasm.

• The starting dose is 0.5-2 mg, I typically start at 0.5 mg for IV hydromorphone.

• These characteristics make hydromorphone appropriate for patients who are hemodynamically stable.

Morphine:

• It comes in IV, IM, SQ, and oral.

• It’s given every 2-4-6 hours or as a continuous infusion or PCA.

• It’s safe to use for hepatic impairment.

• Avoid in advanced renal impairment.

• Similar to Hydromorphone,  it is associated with Histamine release leading to itching, hypotension, and possibly bronchospasm.

• The starting dose is 2-4 mg.

Oxycodone:

• Comes in oral form only.

• Its IR (Instant release) form comes as a single entity of 5 and 10 mg or combined with acetaminophen as 5/325 mg or 10/325 mg given every 4-6 hours as needed.

• It’s safe in advance for hepatic or renal impairment.

Hydrocodone:

• It comes in oral form only.

• The instant release (IR) form comes with acetaminophen, not as a single entity as 5/325 mg or 10/325 mg, and is given every 4-6 hours as needed.

• It’s safe in hepatic impairment.

• Please avoid in advanced renal impairment.

Tramadol

I highly advise against using it for the following reasons:

• It has a very variable analgesic effect based on the speed Tramadol gets metabolized by CYP2DP in the liver. Patients can be slow metabolizers or rapid metabolizers, and the effect greatly varies in between.

• Tramadol’s serotonin effect may lead to seizures or serotonin syndrome.

Let’s sum that up:

• Fentanyl and remifentanil are the most potent opioids followed by hydromorphone followed by morphine.

• Fentanyl and remifentanil are appropriate for hemodynamically unstable patients making them appropriate for ICU patients.

• All opioids are safe for advanced hepatic impairment.

• Hydrocodone and morphine are better avoided in advanced renal impairment.

• Hydrocodone and oxycodone come in oral forms only, while fentanyl and remifentanil come in IV and no oral forms.

• Morphine and Hydromorphone are associated with histamine release leading to itching, hypotension, and bronchospasm. Please avoid giving antihistamines preemptively. If the patient is complaining of itching, nonsedative oral antihistamines should be tried first, if an IV sedative antihistamine is needed, space it out from the time IV morphine or Hydromorphone was given, and make sure the patient is closely monitored.

How to use:

• Patient conditions should guide us on what opioids should we use.

• In critically ill patients, Fentanyl or remifentanil are the ones to go for, they are not appropriate for floor patients given their short duration of action.

• In hemodynamically stable patients, pick oral over IV if feasible, we can use hydrocodone/Acetaminophen or Oxycodone or oxycodone/acetaminophen.

•  If oral opioids are inadequate, then we can use IV morphine or hydromorphone. I typically start with IV morphine unless:

• Advanced renal impairment where hydromorphone is safer to use.

• The patient requires high doses of morphine which means more fluid volume to be given, switching to hydromorphone can reduce the amount of fluid volume.

• The patient insists on having hydromorphone, do the math for the conversion we mentioned earlier, a patient who’s getting 4 mg of IV morphine every 4H as needed can be transitioned into hydromorphone 0.5 mg IV every 4H as needed.

•  IV opioids particularly IV morphine should not be used in ACS (Acute coronary syndrome) unless the chest pain is refractory to nitroglycerine or there is a contraindication to use nitroglycerine.

Weaning of IV opioids

• Wean patients of IV opioids and transition into oral opioids or nonopioid medications as soon as possible.

•  If unable to wean off IV opioids:

1. Add scheduled acetaminophen or NSAIDs.
2. Add scheduled gabapentin.
3. Add scheduled oral opioids if inadequate response to 1&2 and escalate the gabapentin dose.