Epidural Morphine

Article Author:
Andrea Martinez-Velez

Article Editor:
Paramvir Singh

Editors In Chief:
Kranthi Sitammagari
Mayank Singhal

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Abdul Waheed
Khalid Alsayouri
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Mark Pellegrini
James Hughes
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Nazia Sadiq
Hajira Basit
Phillip Hynes

7/16/2019 10:55:48 PM


Morphine was the first opioid approved for spinal administration by the US Food and Drugs Administration (FDA), and it has been the most widely used opioid in clinical practice via this route.[1] Epidural morphine is useful as analgesia, as an adjunct to general anesthesia, or as a sole technique for surgical anesthesia. Morphine sulfate has FDA approval for acute or chronic moderate to severe pain. In 2004, the use of liposome-based extended-release epidural morphine (EREM) also received FDA approval. Due to its delayed peak concentration in the CSF of 3 hours after a single injection, EREM provides up to 48 hours of pain relief after a single-shot epidural administration at the lumbar level.[2] On the other hand, epidural administration of 5 mg of morphine sulfate will provide adequate postoperative analgesia up to 24 hours. Given its long elimination time and its potential to cause delayed adverse effects, neuraxial morphine is not a recommended therapy for ambulatory patients.[3]

Clinical Uses of Epidural Morphine:

  • Perioperative analgesia for several procedures:
    • Abdominal surgeries
    • Thoracic surgeries
    • Vascular surgeries
    • Gynecological surgeries
    • Orthopedic procedures of the lower extremities (knee replacement surgery, hip arthroplasty, etc.)
  • Obstetrics:
    • Cesarean section
    • Labor pain
  • Moderate to severe chronic pain refractory to conservative treatment

Mechanism of Action

Opioids produce analgesia by binding to the mu-opioid receptors distributed throughout the central nervous system (CNS) and peripheral nervous system (PNS) and on many peripheral regions. More specifically, CNS mu-opioid receptors are present in the cerebellum, nucleus accumbens, caudate nucleus of the brain, putamen, cerebral cortex, substantia nigra, and spinal cord.[4] Receptors located in the PNS which contribute to the analgesic properties of opioids include dorsal root ganglion. Opioid agonists bind to G-protein coupled receptors producing an initiation of intracellular transduction pathways that include inhibition of adenylyl cyclase, stimulation of potassium efflux, and inhibition of calcium influx. The net effect of these changes is a reduction in intracellular cAMP, hyperpolarization of the cell, and inhibition of neurotransmitter release.[5]


Epidural morphine can be administered as a single bolus or as a continuous infusion via a catheter. Placing an epidural catheter allows for easier drug titration and seems to induce better quality analgesia.[2] Given its hydrophilic properties, morphine has a slower onset of analgesia and a longer duration of action compared to lipophilic drugs such as fentanyl and sufentanil. The clinical dose of epidural morphine is lower than for intravenous administration due to its good spinal cord selectivity.[1][3] Epidural morphine is about 5 to 10 times more potent than its intravenous form, with clinically used doses of 30 to 100 mcg/kg as a bolus or 0.2 to 0.4 mg/hour as a continuous infusion. Lower doses of morphine are recommended in patients with hepatic or renal dysfunction due to its significantly altered pharmacokinetics. To avoid inadvertent administration of epidural doses into the intrathecal space, always verify proper needle or catheter placement in the epidural space before injecting morphine.

Adverse Effects

Respiratory depression is the most potentially dangerous adverse reaction of opioid administration. The incidence is low with commonly used doses, being dose-dependent for both hydrophilic and lipophilic opioids. The overall risk of respiratory depression after neuraxial opioids is less than 1%, very similar to that of opioids administered via the parenteral route.[2][3] Other adverse reactions of morphine include gastrointestinal effects (constipation, nausea, vomiting), CNS effects (sedation, dizziness), cardiovascular effects (bradycardia, hypotension), urinary retention and pruritus; it remains unclear if these side effects are dose-related. [6] More specifically, the risks of epidural morphine should be considered during pregnancy, particularly if prolonged use. Although the risk of teratogenicity is low, epidural morphine during labor and delivery increases the risk of respiratory depression and bradycardia in both the mother and the neonate.


Epidural morphine, as well as intravenous morphine, should be used with extreme caution in patients with respiratory conditions such as COPD, acute bronchial asthma or upper airway obstruction since it can further decrease the respiratory drive. Additionally, practitioners should avoid using morphine in cases of previous allergy or hypersensitivity reaction to morphine or other opioids. Since the epidural administration of morphine reduces gastroduodenal motility, it should be avoided in patients with confirmed or suspected paralytic ileus. Any absolute contraindication to neuraxial anesthesia, including coagulopathy, infection at the site of puncture or patient refusal, are also contraindications to spinal or epidural opioids.[7]


The therapeutic effect of epidural morphine is assessable through subjective and objective findings. Although the ultimate goal of morphine is pain control, it is important to monitor other parameters like mental status, blood pressure, or respiratory drive. Detection of opioid-induced respiratory depression after neuraxial morphine may be challenging since the respiratory rate may or may not decrease.[2] Capnography, pulse oximetry, respiratory rate, and level of consciousness all require monitoring in all patients receiving opioids. Due to epidural morphine delay onset of action compared to fentanyl or sufentanil, patients should be monitored closely for 18 to 24 hours after neuraxial morphine.[8][9]


A morphine overdose can be potentially lethal due to the risk of respiratory depression. When administered via the epidural route, morphine can cause delayed respiratory depression up to 24 hours after a single injection. If suspected, immediately stop opioids or sedatives and administer intravenous naloxone to reverse the effects of morphine. Naloxone is an opioid antagonist, and its effective dose depends on the amount of opioid received.  In the postoperative patient population, the starting dose of naloxone is 0.04 mg, with increments every 2 minutes if needed to a maximum of 15 mg.[10] Supplemental oxygen should always be available in all patients receiving neuraxial opioids.

Enhancing Healthcare Team Outcomes

The administration of morphine via the epidural route requires an interprofessional healthcare team that includes providers, nurses, and pharmacists. Epidural morphine administration is by an anesthesiologist, nurse anesthetist, or pain specialist for perioperative pain control or chronic refractory pain. A focused history and physical examination is necessary before the administration of neuraxial opioids to identify patients at risk respiratory depression. Given its long duration of action, patients require close monitoring for 18 to 24 hours for the adequacy of ventilation, oxygenation, and level of consciousness. [Level I] Nursing should receive proper training to identify signs of respiratory depression or opioid toxicity so they can alert the physicians when there is a need for intervention. Reversal agents like naloxone should always be available for administration in case of respiratory depression after neuraxial opioid administration. [Level I] THe pharmacist should verify dosing and make recommendations for reversal agents, as well as performing medication reconciliation, and report their findings to the team. The above highlights the necessity of a properly functioning and collaborative interprofessional team approach to ensure optimal patient care when administering and monitoring epidural morphine. [Level V]

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Epidural Morphine - Questions

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A 52-year-old female with a history significant for diabetes mellitus, hypertension, and chronic renal insufficiency is scheduled for right ankle fracture open reduction and internal fixation. Given his history of postoperative nausea and vomiting (PONV) due to sensitivity to anesthesia medication, a scopolamine patch was placed prior to surgery. An epidural catheter was placed for perioperative analgesia, and morphine was administered towards the end of the procedure. Once in PACU, the patient experiences nausea and four episodes of emesis. What is the best treatment for nausea and vomiting caused by epidural morphine?

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A patient comes to the pain management clinic for refractory low back pain. He is taking oral morphine 30 mg every day and would like to try epidural morphine instead. In order to calculate the equivalent conversion factor, epidural morphine delivery is how many times more potent compared to the oral route?

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Epidural Morphine - References


Farquhar-Smith P,Chapman S, Neuraxial (epidural and intrathecal) opioids for intractable pain. British journal of pain. 2012 Feb;     [PubMed]
Mugabure Bujedo B, A clinical approach to neuraxial morphine for the treatment of postoperative pain. Pain research and treatment. 2012;     [PubMed]
Bujedo BM, Current evidence for spinal opioid selection in postoperative pain. The Korean journal of pain. 2014 Jul;     [PubMed]
Streicher JM,Bilsky EJ, Peripherally Acting µ-Opioid Receptor Antagonists for the Treatment of Opioid-Related Side Effects: Mechanism of Action and Clinical Implications. Journal of pharmacy practice. 2017 Sep 25;     [PubMed]
Williams J, Basic Opioid Pharmacology. Reviews in pain. 2008 Mar;     [PubMed]
Liu S,Carpenter RL,Neal JM, Epidural anesthesia and analgesia. Their role in postoperative outcome. Anesthesiology. 1995 Jun;     [PubMed]
Silva M,Halpern SH, Epidural analgesia for labor: Current techniques. Local and regional anesthesia. 2010;     [PubMed]
Lee LA,Caplan RA,Stephens LS,Posner KL,Terman GW,Voepel-Lewis T,Domino KB, Postoperative opioid-induced respiratory depression: a closed claims analysis. Anesthesiology. 2015 Mar;     [PubMed]
Boyer EW, Management of opioid analgesic overdose. The New England journal of medicine. 2012 Jul 12;     [PubMed]
Raft J,Podrez K,Baumann C,Richebé P,Bouaziz H, Postoperative clinical monitoring after morphine administration: a retrospective multicenter practice survey. Current drug safety. 2019 Mar 5;     [PubMed]


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