Epidural Analgesia

Epidural Analgesia

29. T.M., a 69-year-old man, enters the surgical ICU after surgery for colorectal cancer (lower anterior resection, urethral stents, ileorectal pull-through). His pain is managed through a lumbar epidural catheter. What are the benefits and risks of epidural analgesia, and why was this approach to postoperative analgesia chosen for T.M.?

Advantages and Disadvantages

Epidural analgesia can offer superior pain relief over traditional parenteral (IM and IV PCA) analgesia.¹⁵⁸ Continuous epidural infusions offer an advantage over intermittent epidural injections because peak and trough concentrations of drugs are avoided. Epidural catheter placement is an invasive procedure that can result in unintentional dural puncture, causing postdural puncture headache, insertion site inflammation or infection, and, rarely, catheter migration during therapy and epidural hematoma.¹⁵⁵

 

Patient Selection

Epidural analgesia should be chosen based on the need for good postoperative pain relief and reduced perioperative physiological responses. Postoperative pain should be localized at an appropriate level for catheter placement in the lumbar or thoracic location of the epidural space. Patients undergoing abdominal, gynecologic, obstetric, colorectal, urologic, lower limb (e.g., major vascular), or thoracic surgery are excellent candidates for epidural pain management. Absolute contraindications to epidural analgesia include severe systemic infection or infection in the area of catheter insertion, known coagulopathy, significant thrombocytopenia, recent or anticipated thrombolytic therapy, full (therapeutic) anticoagulation, uncorrected hypovolemia, patient refusal, and anatomical abnormalities that make epidural catheter placement difficult or impossible.¹⁵⁹ T.M. is a good candidate for epidural analgesia based on the severity of pain associated with his surgery and the surgical procedure.

 

Choice of Agent and Mechanisms of Action

30. What drug or drug combination can be used for T.M.'s epidural infusion? What are the mechanisms of action of the analgesics commonly administered in the epidural space?

Opioids and local anesthetics are administered alone or in combination in epidural infusions. Opioids in the epidural space are transported by passive diffusion and the vasculature to the spinal cord, where they act at opioid receptors in the dorsal horn. After epidural administration, opioids can reach brainstem sites by cephalad movement in the cerebrospinal fluid. In addition, lipophilic opioids (fentanyl, sufentanil) have substantial systemic absorption from the epidural space.^153,160 Opioids selectively block pain transmission and have no effect on nerve transmission responsible for motor, sensory, or autonomic function.¹⁶¹ Local anesthetics, however, act on axonal nerve membranes crossing through the epidural space to produce analgesia by blocking nerve transmission. Depending on the drug, concentration, and depth of nerve penetration, local anesthetics also produce sensory, motor, or autonomic blockade (see Local Anesthetics section). Table 9-17 describes the spinal actions, efficacy, and adverse effects of opioids and local anesthetics administered by the epidural route.^{154,159,160,162}

 

Table 9-17 A Comparison of the Spinal Actions, Efficacy, and Adverse Effects of Opioids and Local Anestheticsa

Opioids Local Anesthetics Actions Site of action Substantia gelatinosa of dorsal horn of spinal cordb Spinal nerve roots Modalities blocked “Selective” block of pain conduction Blockade of sympathetic pain fibers; can cause loss of sensation and motor function Efficacy Surgical pain Partial relief Complete relief possible Labor pain Partial relief Complete relief Postoperative pain Fair/good relief Complete relief Adverse effects Nausea, vomiting, sedation, confusion, pruritus, constipation/ileus, urinary retention, respiratory depression Hypotension, urinary retention, loss of sensation, loss of motor function resulting in inability to ambulate aEpidurally administered morphine and local anesthetics exert their effects mainly by a spinal mechanism of action; lipophilic opioids such as fentanyl and sufentanil achieve therapeutic plasma concentrations when administered epidurally. bAnd/or other sites where opioid receptor-binding sites are present. Adapted from references 154, 159, 160, and 162.

Most often, opioids and local anesthetics are combined in the same solution because these two classes of drugs act synergistically at two different sites to produce analgesia, allowing the administration of lower doses of each drug to reduce the risk of adverse effects while providing effective analgesia. Table 9-18 lists the drugs, concentrations, and typical infusion rates for epidural administration.^{155,156,160,161,163} Bupivacaine is commonly chosen as the local anesthetic agent because it can preferentially block sensory fibers (producing analgesia) without significantly blocking motor fibers.¹⁵⁵ The choice of opioid is based on pharmacokinetic differences among the available agents. Onset, duration, spread of agent in the spinal fluid (dermatomal spread), and systemic absorption are affected by the lipophilicity of the drug.¹⁶² Highly lipophilic opioids such as fentanyl and sufentanil have a faster onset of action, a shorter duration of action (from a single dose), less dermatomal spread, and much greater systemic absorption. Morphine, which is relatively hydrophilic, has a slower onset of action, longer duration of action, greater dermatomal spread and migration to the brain, and less systemic absorption.^160,162 However, after several hours of epidural infusion, the dermatomal (regional) effect of fentanyl is lost, and analgesia is achieved because of a therapeutic plasma concentration. Morphine, however, retains its spinal mechanism of action.¹⁶⁰ The lipophilicity of hydromorphone is intermediate between fentanyl and morphine. Clinically, hydromorphone has a faster onset and shorter duration than morphine. Its site of action is likely spinal.¹⁶⁴ A

P.9p31

comparison of the pharmacokinetic properties important to epidural opioids is found in Table 9-19.^{155,158,162,163} T.M. should receive a combination of opioid and local anesthetic, such as fentanyl and bupivacaine, as an epidural infusion for postoperative pain management.

Table 9-18 Adult Analgesic Dosing Recommendations for Epidural Infusion

Drug Combinations or Druga Infusion Concentrationb Usual Infusion Rateb Morphine + bupivacaine 25–100 µg/mL (M) 4–10 mL/hr   0.5–1.25 mg/mL (B)   Hydromorphone + bupivacaine 3–20 µg/mL (H) 4–10 mL/hr   0.5–1.25 mg/mL (B)   Fentanyl + bupivacaine 2–10 µg/mL (F) 4–10 mL/hr   0.5–1.25 mg/mL (B)   Sufentanil + bupivacaine 1 µg/mL (S) 4–10 mL/hr   0.5–1.25 mg/mL (B)   Morphine 100 µg/mL 5–8 mL/hr aUse only preservative-free products and preservative-free 0.9% sodium chloride as the admixture solution. bExact concentrations and rates are institution specific. Initial concentration and/or rate often depend on the age and general condition of the patient. M, morphine; B, bupivacaine; H, hydromorphone; F, fentanyl; S, sufentanil. Adapted from references 155, 156, 160, 161, and 163.

 

31. Fentanyl/bupivacaine is chosen for T.M. How should this be prepared, and what infusion rate should be chosen?

Fentanyl and bupivacaine are commonly admixed in 0.9% sodium chloride (usual concentration ranges are found in Table 9-18). Concentrations are often institution specific and depend on the rate of administration. Preservative-free preparations of each drug should be used because neurologic effects are possible with inadvertent subdural administration of large amounts of benzyl alcohol or other preservatives. Strict aseptic technique should be used when admixing and administering an epidural solution.

The rate of administration is chosen empirically based on the anticipated analgesic response, the concentration of opioid in the admixture, and the potential for adverse effects. Usually, a rate of 4 to 10 mL/hour is adequate; the epidural space can safely handle up to approximately 20 mL/hour of fluid. An initial infusion rate of 5 to 8 mL/hour would be reasonable for T.M., with titration based on efficacy and adverse effects.

 

Adverse Effects

32. Two hours after initiation of his fentanyl/bupivacaine epidural infusion, T.M. experiences discomfort in the form of an itchy feeling on his nose, torso, and limbs. Is this related to his epidural infusion?

Table 9-19 Pharmacokinetic Comparison of Common Epidural Opioid Analgesics

Agent Partition Coefficienta Onset of Action of Bolus (minutes) Duration of Action of Bolus (hours) Dermatomal Spread Fentanyl (Sublimaze) 955 5 3–6 Narrow Hydromorphone (Dilaudid) 525 15 6–17 Intermediate Morphine Sulfate (Duramorph) 1 30 12–24 Wide Sufentanil (Sufenta) 1,737 5 4–7 Narrow aOctanol/water partition coefficient; used to assess lipophilicity; higher numbers indicate greater lipophilicity. Adapted from references 155, 158, 162, and 163.

 

Pruritus has been associated with almost all opioids, with a significantly greater frequency when the opioid is administered as an epidural infusion rather than by IV administration.¹⁶⁵ This effect is usually seen within 2 hours and is probably dose related. It generally subsides as the opioid effect wears off and can be more of a problem with continuous epidural administration of opioids or when opioids are administered via PCA. Although pruritus from opioids is probably µ-receptor mediated and not histamine mediated,¹⁶⁶ antihistamines (e.g., diphenhydramine) can provide symptomatic relief. Alternatively, very small doses of opioid antagonists (e.g., naloxone 0.04 mg) can be used to effectively reverse opioid adverse effects, such as pruritus, but not analgesia. Due to naloxone's short duration of action, repeat doses or a continuous infusion may be necessary.

Other adverse effects possible with epidural opioids include nausea, vomiting, sedation, confusion, constipation, ileus, urinary retention, and respiratory depression. Although rare, respiratory depression from epidural opioids is the most dangerous adverse effect. Respiratory depression can occur as long as 12 to 24 hours after a single bolus of morphine^160,162 or within hours to 6 days after beginning a continuous infusion of fentanyl/bupivacaine.¹⁶⁷ Typically, regular assessments of sedation level and rate and depth of respirations safely detect respiratory depression from opioids.^148,160 As with parenteral opioid administration, risk factors for opioid-related respiratory depression include severe underlying systemic disease or pre-existing respiratory compromise, concomitant use of other sedative-hypnotics (e.g., benzodiazepines, opioids administered by another route), and older age. As a result, reduced doses should be used in patients with these risk factors. Adverse effects of epidural local anesthetics include hypotension, urinary retention, lower limb paresthesias or numbness, and lower limb motor block. Depending on the degree of numbness and motor block, the patient may have difficulty ambulating. Monitoring for efficacy and adverse effects of epidural analgesia should include pain intensity and quality, response to treatment, number of on-demand requests (if PCA is being used), analgesic consumption, BP, heart rate, respiratory depth and rate, level of sedation, urinary output, presence of numbness/tingling, inability to raise legs or flex knees/ankles (lumbar epidural placement), and temperature.

 

Adjunctive Ketorolac Use

33. On the second postoperative day, T.M. is able to rest comfortably when undisturbed, while receiving treatment with a lumbar epidural infusion of fentanyl 3 µg/mL and bupivacaine 1.25 mg/mL at a rate of 8 mL/hour. However, when he is moved at the change of each nursing shift, he complains of significant pain. Increasing the rate of his epidural infusion was tried, but caused unacceptable pruritus and sedation. How can T.M.'s intermittent pain needs be addressed?

The use of additional analgesics for breakthrough pain may be necessary in patients receiving continuous epidural infusion. T.M.'s intermittent pain could be managed by patient-controlled epidural analgesia. Like IV PCA, patient-activated epidural boluses can be administered to control pain during movement. Alternatively, ketorolac, an injectable NSAID, may be considered for T.M.; it does not contribute to respiratory depression, sedation, or pruritus and effectively treats moderate-to-severe pain. The analgesic effects of NSAIDs are additive with the opioids and can lower postoperative pain scores. Patient selection for ketorolac therapy should consider renal function, plasma volume and electrolyte status, GI disease, risk of bleeding, and concomitant drugs and therapies such as epidural analgesia.

 

Adjunctive Anticoagulant Administration

34. The surgeon has determined that T.M. is at risk for developing postoperative venous thromboembolism. Enoxaparin 40 mg SC QD has been ordered postoperatively. What are the risks of enoxaparin in this situation? What are reasonable precautions?

Prolonged therapeutic anticoagulation appears to increase the risk of epidural and spinal hematoma formation, which can lead to long-term or permanent paralysis. Administration of antiplatelet or anticoagulant drugs in combination with low-molecular-weight heparin (LMWH) results in an even greater risk of perioperative hemorrhagic complications, including spinal hematoma. These findings have led to concern for the safety of spinal and epidural anesthesia and analgesia in patients receiving LMWH. Important considerations for managing a patient being administered LMWH and receiving continuous epidural analgesia are (a) the time of catheter placement and removal relative to the timing (and peak effect) of LMWH administration, (b) total daily dose of LMWH, and (c) the dosing schedule of LMWH.¹⁶⁸ For T.M., the epidural catheter is already in place and the LMWH is started postoperatively as a single daily dose. It is safe to leave the epidural catheter in place as long as the first dose of LMWH is administered 6 to 8 hours postoperatively. The second dose should be administered no sooner than 24 hours after the first dose. The timing of the catheter removal is of the utmost importance; it should be delayed for at least 10 to 12 hr after the last dose of LMWH, with subsequent dosing occurring a minimum of 2 hours after the catheter has been removed. There may be a greater risk of spinal hematoma when LMWH is administered twice a day. For that reason, if Q 12 hr enoxaparin is required, the catheter should be removed, and the first dose of LMWH administered at least 2 hours after catheter removal.¹⁶⁸ Because T.M. is receiving prophylactic daily enoxaparin, his catheter should be removed no earlier than 10 hours after his last dose of enoxaparin, with his next dose administered no earlier than 2 hours after catheter removal.

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