Amputation Anesthesia: Pain Management

• Anesthetic management for amputation patients hinges on addressing coexisting diseases.
• A multimodal approach is needed for prevention of central sensitization and chronic pain.
• Phantom limb pain, potentially with stump pain, is the most common postoperative complication.

Pathophysiology

• Many above the knee amputation (AKA) patients have conditions like diabetes and cardiovascular disease.
• A portion of patients undergoing amputation are otherwise healthy individuals experiencing trauma to the lower extremity.
• Pain involves sensation, influenced by individual, psychological, and sociocultural variance.
• Tissue injury releases chemicals like bradykinins and histamine, activating the arachidonic acid cascade and causing inflammation.
• Inflammation amplifies the pain stimulus by further stimulating the peripheral nerve.
• Transduction refers to mechanical stimulation converting to electrical activity, or an action potential.
• Nociceptive fibers can be stimulated by multiple modalities.
• A and B fibers are myelinated while C fibers aren't.
• Myelination affects conduction speed; A fibers transmit "sharp" pain quickly.
• Unmyelinated C fibers transmit "dull" or "aching" pain slowly.
• Transmission is the process where electrical impulses are conducted through a nerve under normal conditions.
• Afferent nerves enter the dorsal horn, terminating in lamina V or I.
• Nerve branches end in lamina II and III (substantia gelatinosa), modulating pain via inhibitory neurons.
• Most axons ascend in the spinothalamic tract, crossing to the opposite side.
• Axons terminate in the thalamus or somatosensory cortex, where pain is perceived.

Perioperative Considerations

• The incidence of chronic pain after amputation is reportedly as high as 80%.
• Preventing the "wind-up" phenomenon is important for preventing intractable pain with long-lasting effects.
• Surgical trauma and inflammation create significant afferent stimulation leading to central sensitization.
• Acute or postoperative pain and inflammation can have long-lasting effects due to changes in the peripheral and central nervous system.
• The central nervous system displays plasticity, meaning it is a dynamic system.
• The inflammatory process leads to reduced thresholds of peripheral neurons and other changes in afferent neurons.
• Sensory input from the periphery increases the excitability of spinal neurons in the central nervous system.
• Peripheral and central sensitization is referred to as "wind-up" and can lead to intractable pain.
• Central sensitization involves physiologic changes in the nervous system that lead to allodynia, hyperalgesia, decreased pain threshold, and referred pain.
• Changes in the N-methyl-D-aspartate (NMDA) receptor can result in central sensitization
• Ectopic neuronal firing can result in central sensitization
• Changes in the gene expression of the sodium channel can result in central sensitization
• Sensitization of the nociceptive receptor can result in central sensitization
• Preoperative midazolam administration is recommended because this procedure is associated with anxiety; an opioid may also be considered.
• Regularly scheduled medications should be continued preoperatively.
• Neuraxial anesthesia is recommended for anesthesia and analgesia unless contraindicated.
• Evidence suggests that an epidural catheter insertion followed by a 48-hour continuous bupivacaine infusion should be placed before the amputation procedure to improve postoperative outcomes.

Intraoperative Considerations

• A multimodal technique should be utilized to meet the patient's anesthetic goals.
• Titration of medications is paramount to a successful anesthetic.
• Gastric ulceration can occur, especially if NSAIDs are taken at high doses and on a routine basis.
• Prostaglandins created by the COX-2 enzyme mediate pain and have been implicated in increasing edema formation resulting from surgical trauma.
• Adjuncts that may be considered as part of a balanced anesthetic:
  • Ketamine infusion: 0.1 to 0.3 mg/kg/hr IV
  • Dexmedetomidine 0.5 to 1.0 mcg/kg IV
  • Opioids: titrated to the observed analgesic effect

Postoperative Considerations

• Meeting the psychological needs of the patient postoperatively is important.
• Providing a calm, quiet environment, especially if the patient exhibits signs of posttraumatic stress disorder, is vital.
• Multidisciplinary support, as well as family support, is optimal to aid the patient to deal with the significant emotional component of the loss of limb and loss of function.
• The epidural infusion after surgery may contain a solution that will provide adequate sensory blockade.
• Bupivacaine (0.125% to 0.25%), with or without adjuncts, may be used in the epidural infusion.
• Adjuncts to the epidural infusion include fentanyl 2 mcg/mL or hydromorphone 20 mcg/mL.
• The epidural infusion should be continued unless anticoagulation is required.
• If anticoagulation is planned and the epidural will be discontinued, a peripheral nerve catheter should be considered.
• A femoral nerve catheter and a sciatic catheter are required to provide adequate coverage for the amputee.
• The peripheral nerve catheters can be placed preoperatively, but if the epidural is to be used for the first 24 hours, the catheters can be placed on the first postoperative day.
• Multimodal therapy should be resumed as soon as possible after surgery, with attention to the time frame that the patient is tolerating oral medications.
• IV agents should be utilized to maintain multimodal therapy until the patient can take oral medications.
• If there is breakthrough pain, patient-controlled analgesia (PCA) may be necessary.
• If significant opioid side effects are present (nausea, respiratory depression), it is possible to add ketamine to the PCA.

Multimodal Analgesia

• Opioids are the mainstay for treating pain but have undesirable side effects like nausea, vomiting, respiratory depression, sedation, pruritus, urinary retention, and sleep disturbances.
• The goal of multimodal analgesia is to improve analgesia and reduce opioid-related side effects.
• Multimodal analgesia targets different aspects of the pain pathway.
• Multimodal analgesia utilizes the synergistic effects of combinations of medication to provide sufficient analgesia and minimize side effects.
• Prolonged use of opioids can cause nausea and vomiting, respiratory depression, sedation, pruritus, urinary retention, and sleep disturbances.
• Increasing opioid dosages are often required to achieve the same level of analgesia, this is known as tolerance.
• Prolonged use of opioids is associated with opioid-induced hypersensitivity.
• Spinal cord changes after prolonged opioid doses are similar to those in models of neuropathic pain.
• Prolonged opioid use is associated with hormonal changes and immunosuppression.
• Minimizing the dosages and length of opioid therapy is therefore desirable.
• Multimodal analgesic regimens for orthopedic surgery include local anesthetics, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, NMDA receptor antagonists, and opioids.
• Alpha-2 agonists have analgesic actions at peripheral, spinal, and brainstem sites where alpha-2 adrenoreceptors are located.
• Alpha-2 agonists are valuable adjuncts for treating sympathetically mediated pain by inhibiting the release of norepinephrine from the alpha-2 adrenoreceptors.
• Clonidine enhances both peripheral and neuraxial blockade and can reduce opioid requirements after orthopedic surgery when added to epidural infusion.
• Dexmedetomidine is an alpha-2 agonist that is an option, as administering this drug can be useful to decrease the physiological stress response associated with surgery and decrease postoperative pain.
• Lower doses of ketamine are useful for pain management with minimal psychomimetic effects
• Memantine is an alternative to ketamine that can be administered orally and has a lower incidence of undesirable side effects.
• NMDA receptors are located on primary afferents, interneurons, and projection neurons.
• Gabapentin is an anticonvulsant that binds to the a28 subunit of voltage-gated calcium channels, inhibiting the calcium current in sensory neurons.
• Gabpentin may interact with the NMDA receptor complex
• Gabapentin is an important adjunct for preemptive analgesia.
• Tissue injury activates the arachidonic acid cascade, leading to prostaglandin production.
• Prostaglandins sensitize nociceptors, leading to hyperalgesia.
• NSAIDs inhibit cyclooxygenase types 1 and 2 (COX-1 and COX-2), decreasing prostaglandin production.
• COX-1-created prostaglandins are necessary for homeostasis and contribute to adequate bronchial and renal vascular tone, normal platelet function, and the gastric barrier.
• NSAID side effects, such as bronchospasm, renal insufficiency, and bleeding, are associated with inhibited prostaglandin production that is necessary for physiologic functioning.
• NSAIDs inhibit prostaglandin production in the periphery and spinal cord, reducing inflammation and pain after surgery.
• Acetaminophen may inhibit prostaglandin production in the central nervous system, possibly mediated by inhibition of a COX-3 receptor.
• Acetaminophen can decrease pain and inflammation after surgery without the side effects of COX-2 inhibitors.

Anesthetic management for amputation patients requires a multimodal approach to prevent chronic pain and central sensitization. Phantom limb pain is a common complication. Many patients have co-existing conditions like diabetes and cardiovascular disease.