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Pharmacological Interventions
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Pharmacological interventions in pain management include acetaminophen, cyclooxygenase (COX) inhibitors, opioids, antidepressants, neuroleptic agents, anticonvulsants, corticosteroids, and systemic administration of local anesthetics.
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Acetaminophen (paracetamol) is an oral analgesic and antipyretic agent that recently has become available in the United States as an intravenous preparation (Ofirmev) for inpatient use. It inhibits prostaglandin synthesis but lacks significant antiinflammatory activity. Acetaminophen has few side effects but is hepatotoxic at high doses. The recommended adult maximum daily limit is 3000 mg/d, reduced from a previously recommended limit of 4000 mg/d. Isoniazid, zidovudine, and barbiturates can potentiate acetaminophen toxicity.
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Nonsteroidal Antiinflammatory Drugs (NSAIDs)
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Nonopioid oral analgesics include salicylates, acetaminophen, and NSAIDs (see Table 47-11). NSAIDs inhibit prostaglandin synthesis (COX). Prostaglandins sensitize and amplify nociceptive input, and blockade of their synthesis results in the analgesic, antipyretic, and antiinflammatory properties characteristic of NSAIDs. At least two types of COX are recognized. COX-1 is constitutive and widespread throughout the body, but COX-2 is expressed primarily with inflammation. Some types of pain, particularly pain that follows orthopedic and gynecological surgery, respond very well to COX inhibitors. COX inhibitors likely have important peripheral and central nervous system actions. Their analgesic action is limited by side effects and toxicity at higher doses. Selective COX-2 inhibitors, such as celecoxib, appear to have lower toxicity, particularly gastrointestinal side effects. Moreover, COX-2 inhibitors do not interfere with platelet aggregation. The COX-2 inhibitor rofecoxib increases the risk of cardiovascular complications; as a result, it has been taken off of the market in the United States.
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All of the nonopioid oral analgesic agents are well absorbed enterally. Food delays absorption but otherwise has no effect on bioavailability. Because most of these agents are highly protein bound (>80%), they can displace other highly bound drugs such as warfarin. All undergo hepatic metabolism and are renally excreted. Dosages should therefore be reduced, or alternative medications selected, in patients with hepatic or renal impairment.
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The most common side effects of aspirin (acetylsalicylic acid, ASA) and other NSAIDs are stomach upset, heartburn, nausea, and dyspepsia; some patients develop ulceration of the gastric mucosa, which appears to be due to inhibition of prostaglandin-mediated mucus and bicarbonate secretion. Diclofenac is available as both an oral preparation and a topical gel or patch that may be less likely to contribute to gastric distress.
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Other side effects of NSAIDs include dizziness, headache, and drowsiness. With the exception of selective COX-2 inhibitors, all other COX inhibitors induce platelet dysfunction. Aspirin irreversibly acetylates platelets, inhibiting platelet adhesiveness for 1-2 weeks, whereas the antiplatelet effect of other NSAIDs is reversible and lasts approximately five elimination half-lives (24-96 h). This antiplatelet effect does not appear to appreciably increase the incidence of postoperative hemorrhage following most outpatient procedures. NSAIDs can exacerbate bronchospasm in patients with the triad of nasal polyps, rhinitis, and asthma. ASA should not be used in children with varicella or influenza infections because it may precipitate Reye’s syndrome. Lastly, NSAIDs can cause acute renal insufficiency and renal papillary necrosis, particularly in patients with underlying renal dysfunction.
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Antidepressants are most useful for patients with neuropathic pain. These medications demonstrate an analgesic effect that occurs at a dose lower than that needed for antidepressant activity, and both of these actions are due to blockade of presynaptic reuptake of serotonin,
norepinephrine, or both. Older tricyclic agents appear to be more effective analgesics than selective serotonin reuptake inhibitors (SSRIs). Serotonin and
norepinephrine reuptake inhibitors (SNRIs) may provide the most favorable balance between analgesic efficacy and side effects. Antidepressants potentiate the action of opioids and frequently help normalize sleep patterns.
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All antidepressant medications undergo extensive first-pass hepatic metabolism and are highly protein bound. Most are highly lipophilic and have large volumes of distribution. Elimination half-lives of most of these medications vary between 1 and 4 days, and many have active metabolites. Available agents differ in their side effects (see Table 47-13), which include antimuscarinic effects (dry mouth, impaired visual accommodation, urinary retention, and constipation), antihistaminic effects (sedation and increased gastric pH), α-adrenergic blockade (orthostatic hypotension), and a quinidine-like effect (atrioventricular block, QT prolongation, torsades de pointes).
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Serotonin & Norepinephrine Reuptake Inhibitors (SNRIs)
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Milnacipran, along with the SNRI duloxetine and the anticonvulsant pregabalin, has also been approved in the United States by the FDA for the treatment of fibromyalgia. It has an elimination half-life of 8 h, is minimally metabolized by the liver, and is primarily excreted unchanged in the urine.
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Duloxetine (Cymbalta) is useful in the treatment of neuropathic pain, depression, and fibromyalgia. It has a half-life of 12 h, is metabolized by the liver, and most of its metabolites are excreted in the urine.
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Absolute and relative contraindications for the use of SNRIs include known hypersensitivity, usage of other drugs that act on the central nervous system (including monoamine oxidase inhibitors), hepatic and renal impairment, uncontrolled narrow-angle glaucoma, and suicidal ideation. Common side effects include nausea, headache, dizziness, constipation, insomnia, hyperhydrosis, hot flashes, vomiting, palpitations, dry mouth, and hypertension.
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Neuroleptic medications may occasionally be useful for patients with refractory neuropathic pain, and may be most helpful in patients with marked agitation or psychotic symptoms. The most commonly used agents are fluphenazine, haloperidol, chlorpromazine, and perphenazine. Their therapeutic action appears to be due to blockade of dopaminergic receptors in mesolimbic sites. Unfortunately, the same action in nigrostriatal pathways can produce undesirable extrapyramidal side effects, such as masklike facies, a festinating gait, cogwheel rigidity, and bradykinesia. Some patients also develop acute dystonic reactions such as oculogyric crisis and torticollis. Long-term side effects include akathisia (extreme restlessness) and tardive dyskinesia (involuntary choreoathetoid movements of the tongue, lip smacking, and truncal instability). Like antidepressants, many of these drugs also have antihistaminic, antimuscarinic, and α-adrenergic-blocking effects.
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Antispasmodics & Muscle Relaxants
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Antispasmodics may be helpful for patients with musculoskeletal sprain and pain associated with spasm or contractures. Tizanidine (Zanaflex) is a centrally acting α2-adrenergic agonist used in the treatment of muscle spasm in conditions such as multiple sclerosis, low back pain, and spastic diplegia. Cyclobenzaprine (Flexeril) also may be effective for these conditions. Its precise mechanism of action is unknown.
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Baclofen (Gablofen, Lioresal), a GABAB agonist, is particularly effective in the treatment of muscle spasm associated with multiple sclerosis or spinal cord injury when administered by continuous intrathecal drug infusion. Abrupt discontinuation of this medication has been associated with fever, altered mental status, pronounced muscle spasticity or rigidity, rhabdomyolysis, and death.
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Glucocorticoids are extensively used in pain management for their antiinflammatory and possibly analgesic actions. They may be given topically, orally, or parenterally (intravenously, subcutaneously, intrabursally, intraarticularly, or epidurally). Table 47-15 lists the most commonly used agents, which differ in potency, relative glucocorticoid and mineralocorticoid activities, and duration or action. Large doses or prolonged administration result in significant side effects. Excess glucocorticoid activity can produce hypertension, hyperglycemia, increased susceptibility to infection, peptic ulcers, osteoporosis, aseptic necrosis of the femoral head, proximal myopathy, cataracts, and, rarely, psychosis. Patients with diabetes may have elevated blood glucose levels after corticosteroid injections. Patients can also develop the physical features characteristic of Cushing’s syndrome. Excess mineralocorticoid activity causes sodium retention and hypokalemia, and can precipitate congestive heart failure.
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Many corticosteroid preparations are suspensions, rather than solutions, and the relative particulate size of a given glucocorticoid suspension may affect the risk of neural damage due to arterial occlusion when accidental arterial injection occurs. Because of the relatively small size of its suspension particles, dexamethasone is becoming the preferred corticosteroid for injection procedures involving relatively vascular areas, such as the head and neck region.
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Anticonvulsant medications are useful for patients with neuropathic pain, especially trigeminal neuralgia and diabetic neuropathy. These agents block voltage-gated calcium or sodium channels and can suppress the spontaneous neural discharges that play a major role in these disorders. The most commonly utilized agents are
phenytoin (Dilantin),
carbamazepine (Tegretol), valproic acid (Depakene, Stavzor),
clonazepam (Klonopin), and
gabapentin (Neurontin) (Table 47-14).
Pregabalin (Lyrica) is a newer agent that has been approved for the treatment of diabetic peripheral neuropathy and fibromyalgia but is widely prescribed for all forms of neuropathic pain.
Lamotrigine (Lamictal) and
topiramate (Topamax) may also be effective. All are highly protein bound and have relatively long half-lives.
Carbamazepine (Carbatrol, Equetro, Tegretol) has a slow and unpredictable absorption, which requires monitoring of blood levels for optimal efficacy.
Phenytoin may be effective, but there is a possible side effect of gum hyperplasia.
Levetiracetam (Keppra) and
oxcarbazepine (Trileptal) have been used as adjuvant pain therapies.
Gabapentin and
pregabalin may also be effective adjuvants for the treatment of acute postoperative pain.
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Systemic infusion of local anesthetic medication produces sedation and central analgesia and is occasionally used in the treatment of patients with neuropathic pain. The resultant analgesia may outlast the pharmacokinetic profile of the local anesthetic and break the “pain cycle.” Lidocaine, procaine, and chloroprocaine are the most commonly used agents. They are given either as a slow bolus or by continuous infusion. Lidocaine is given by infusion over 5-30 min for a total of 1-5 mg/kg. Procaine, 200-400 mg, can be given intravenously over the course of 1-2 h, whereas chloroprocaine (1% solution) is infused at a rate of 1 mg/kg/min for a total of 10-20 mg/kg. Monitoring by qualified medical personnel should include electrocardiographic data, blood pressure, respiration, pulse oximetry, and mental status, and full resuscitation equipment should be immediately available. Signs of toxicity, such as tinnitus, slurring of speech, excessive sedation, or nystagmus, necessitate slowing or discontinuing the infusion to avoid the progression to seizures.
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Patients who do not respond satisfactorily to anticonvulsants but respond to intravenous local anesthetics may benefit from chronic oral antiarrhythmic therapy. Mexiletine (150-300 mg every 6-8 h) is a class 1B antiarrhythmic that is commonly used and generally well tolerated.
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A 5% lidocaine transdermal patch (Lidoderm) containing 700 mg of lidocaine has been approved for the treatment of PHN. One to three patches may be applied to dry, intact skin, alternating 12 h on, then 12 h off. Topical lidocaine preparations, in concentrations up to 5%, may be helpful in the treatment of some neuropathic pain conditions.
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α2-Adrenergic Agonists
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The primary effect of α2-adrenergic agonists is activation of descending inhibitory pathways in the dorsal horn. Epidural and intrathecal α2-adrenergic agonists are particularly effective in the treatment of neuropathic pain and opioid tolerance. Clonidine (Catapres), a direct-acting α2-adrenergic agonist, is effective as an adjunctive medication in the treatment of severe pain. When administered orally, the dosage is 0.1-0.3 mg twice daily; a transdermal patch (0.1-0.3 mg/d) is also available and is usually applied for 7 d. When used in combination with a local anesthetic or opioid in an epidural or intrathecal infusion, clonidine may contribute to a synergistic or prolonged analgesic effect, especially for neuropathic pain.
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The most commonly prescribed oral opioid agents are codeine, oxycodone, and hydrocodone. They are easily absorbed, but hepatic first-pass metabolism limits systemic delivery. Like other opioids, they undergo hepatic biotransformation and conjugation before renal elimination. Codeine is transformed by the liver into morphine. The side effects of orally administered opioids are similar to those of systemic opioids. When prescribed on a fixed schedule, stool softeners or laxatives are often indicated. Tramadol (Rybix, Ryzolt, Ultram) is a synthetic oral opioid that also blocks neuronal reuptake of norepinephrine and serotonin. It appears to have the same efficacy as the combination of codeine and acetaminophen but, unlike others, it is associated with significantly less respiratory depression and has little effect on gastric emptying.
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Moderate to severe cancer pain is usually treated with an immediate-release morphine preparation (eg, liquid morphine, Roxanol, 10-30 mg every 1-4 h). These preparations have an effective half-life of 2-4 h. Once the patient’s daily requirements are determined, the same dose can be given in the form of a sustained-release morphine preparation (MS Contin or Oramorph SR), which is dosed every 8-12 h. The immediate-release preparation is then used only for breakthrough pain (PRN). Oral transmucosal fentanyl lozenges (Actiq, 200-1600 mcg) can also be used for breakthrough pain. Excessive sedation can be treated with dextroamphetamine (Dexedrine, ProCentra) or methylphenidate (Ritalin), 5 mg in the morning and 5 mg the early afternoon. Most patients require a stool softener. Nausea may be treated with transdermal scopolamine, oral meclizine, or metoclopramide. Hydromorphone (Dilaudid) is an excellent alternative to morphine, particularly in elderly patients (because of fewer side effects) and in patients with impaired renal function. Methadone (Dolophine) is reported to have a half-life of 15-30 h, but clinical duration is shorter and quite variable (usually 6-8 h).
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Patients who experience opioid tolerance require escalating doses of opioid to maintain the same analgesic effect. Physical dependence manifests in opioid withdrawal when the opioid medication is either abruptly discontinued or the dose is abruptly and significantly decreased. Psychological dependence, characterized by behavioral changes focusing on drug craving, is rare in cancer patients. The development of opioid tolerance is highly variable but results in some desirable effects such as decreased opioid-related sedation, nausea, and respiratory depression. Unfortunately, many patients continue to suffer from constipation. Physical dependence occurs in all patients receiving large doses of opioids for extended periods. Opioid withdrawal phenomena can be precipitated by the administration of opioid antagonists. Future concomitant use of peripheral opioid antagonists that do not cross the blood-brain barrier, such as
methylnaltrexone (Relistor) and
alvimopan (Entereg), may help reduce systemic side effects without significantly affecting analgesia.
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Tapentadol (Nucynta), a μ-opioid receptor agonist that also has norepinephrine reuptake inhibition properties, has recently been introduced for the management of acute and chronic pain. This opioid may be associated with less nausea and vomiting and less constipation. It should not be used concomitantly with monoamine oxidase inhibitors due to potentially elevated levels of norepinephrine.
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Propoxyphene with and without acetaminophen (Darvocet and Darvon) was withdrawn from the U.S. market in 2010 due to the risk of cardiac toxicity.
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Parenteral Opioid Administration
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Intravenous, intraspinal (epidural or intrathecal), or transdermal routes of opioid administration must be utilized when the patient fails to adequately respond to, or is unable to tolerate, oral regimens. However, when the patient’s pain increases significantly, or changes markedly in quality, it is equally important to reevaluate the patient for adequacy of pain diagnosis and for the potential of disease progression. In patients with cancer, adjunctive treatments such as surgery, radiation, chemotherapy, hormonal therapy, and neurolysis may be helpful. Intramuscular opioid administration is rarely optimal because of variability in systemic absorption and resultant delay and variation in clinical effect.
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Intravenous Opioid Therapy
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Parenteral opioid therapy is usually best accomplished by intermittent or continuous intravenous infusion, or both, but can also be given subcutaneously. Modern portable infusion devices have patient-controlled analgesia (PCA) capability, allowing the patient to self-treat for breakthrough pain.
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Spinal Opioid Therapy
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The use of intraspinal opioids is an excellent alternative for patients obtaining poor relief with other analgesic techniques or who experience unacceptable side effects. Epidural and intrathecal opioids offer pain relief with substantially lower total doses of opioid and fewer side effects. Continuous infusion techniques reduce drug requirements (compared with intermittent boluses), minimize side effects, and decrease the likelihood of catheter occlusion. Myoclonic activity may be occasionally observed with intrathecal morphine or hydromorphone.
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Epidural or intrathecal catheters can be placed percutaneously or implanted to provide long-term effective pain relief. Epidural catheters can be attached to lightweight external pumps that can be worn by ambulatory patients. A temporary catheter must be inserted first to assess the potential efficacy of the technique. Correct placement of the permanent catheter should be confirmed using fluoroscopy with contrast dye. Completely implantable intrathecal catheters with externally programmable pumps can also be used for continuous infusion (Figure 47-6). The reservoir of the implanted pump (Figure 47-7) is periodically refilled percutaneously. Implantable systems are most appropriate for patients with a life expectancy of several months or longer, whereas tunneled epidural catheters are appropriate for patients expected to live only weeks. Formation of an inflammatory mass (granuloma) at the tip of the intrathecal catheter can occur and may reduce efficacy.
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The most frequently encountered problem associated with intrathecal opioids is tolerance. Generally a slow phenomenon, tolerance may develop rapidly in some patients. In such instances, adjuvant therapy must be used, including the intermittent use of local anesthetics or a mixture of opioids with local anesthetics (bupivacaine or ropivacaine 2-24 mg/d), clonidine (2-4 mcg/kg/h or 48-800 mcg/d, respectively), or the GABA agonist baclofen. Clonidine is particularly useful for neuropathic pain. In high doses, it is more likely to be associated with hypotension and bradycardia.
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Complications of spinal opioid therapy include local skin infection, epidural abscess, meningitis, and death or permanent injury from pump programming or drug dilution errors. Superficial infections can be reduced by the use of a silver-impregnated cuff close to the exit site. Other complications of spinal opioid therapy include epidural hematoma, which may become clinically apparent either immediately following catheter placement or several days later, and respiratory depression. Respiratory depression secondary to spinal opioid overdose can be treated by decreasing the pump infusion rate to its lowest setting and initiating a naloxone intravenous infusion.
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Transdermal fentanyl (Duragesic patch) is an alternative to sustained-release oral morphine and oxycodone preparations, particularly when oral medication is not possible. The currently available patches are constructed as a drug reservoir that is separated from the skin by a microporous rate-limiting membrane and an adhesive polymer. A very large quantity of fentanyl (10 mg) provides a large force for transdermal diffusion. Transdermal fentanyl patches are available in 25, 50, 75, and 100 mcg/h sizes that provide drug for 2-3 days. The largest patch is equivalent to 60 mg/d of intravenous morphine. The major obstacle to fentanyl absorption through the skin is the stratum corneum. Because the dermis acts as a secondary reservoir, fentanyl absorption continues for several hours after the patch is removed. The transdermal route avoids hepatic first-pass metabolism.
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Major disadvantages of the transdermal route are its slow rate of drug delivery onset and the inability to rapidly change dosage in response to changing opioid requirements. Blood fentanyl levels rise and reach a plateau in 12-40 h, providing average concentrations of 1, 1.5, and 2 ng/mL for the 50, 75, and 100 mcg/h patches, respectively. Large inter-patient variability results in actual delivery rates ranging from 50 to 200 mcg/h. This formulation is popularly “diverted” for nonmedical uses and has been the cause of numerous deaths from “recreational” pharmacology.
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Botulinum Toxin (Botox)
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OnabotulinumtoxinA (Botox) injection has been increasingly utilized in the treatment of pain syndromes. Studies support its use in the treatment of conditions associated with involuntary muscle contraction (eg, focal dystonia and spasticity), and it is approved by the FDA for prophylactic treatment of chronic migraine headache. This toxin blocks acetylcholine released at the synapse in motor nerve endings but not sensory nerve fibers. Proposed mechanisms of analgesia include improved local blood flow, relief of muscle spasms, and release of muscular compression of nerve fibers
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Diagnostic & Therapeutic Blocks
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Local anesthetic nerve blocks are useful in delineating pain mechanisms, and they play a major role in the management of patients with acute or chronic pain. Pain relief following diagnostic nerve blockade often carries favorable prognostic implications for a subsequent therapeutic series of blocks. Although the utility of differential nerve blocks in distinguishing between somatic and sympathetic mechanisms has been questioned, this technique can identify patients exhibiting a placebo response and those with psychogenic mechanisms. In selected patients, “permanent” neurolytic nerve blocks may be appropriate.
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The efficacy of nerve blocks is presumably due to interruption of afferent nociceptive activity. This is in addition to, or in combination with, blockade of afferent and efferent limbs of abnormal reflex activity involving sympathetic nerve fibers and skeletal muscle innervation. The pain relief frequently outlasts (by hours up to several weeks) the known pharmacological duration of the agent employed. Selection of the type of block depends on the location of pain, its presumed mechanism, and the skills of the treating physician. Local anesthetic solutions may be applied locally (infiltration), or at a specific peripheral nerve, somatic plexus, sympathetic ganglia, or nerve root. The local anesthetic may also be applied centrally in the neuraxis.
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Ultrasound-Guided Procedures
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The use of ultrasound in interventional pain medicine has increased over the past decade due to its utility in visualizing vascular, neural, and other anatomic structures; its role as an alternative to the use of fluoroscopy and iodine-based contrast agents; and progressive improvements in technology leading to better visual images and greater simplicity of use. Most notably, ultrasound has become very useful for visualizing blood vessels and potentially decreasing the incidence of intravascular injection of particulate steroid medications. It may also be helpful in decreasing the risk of pneumothorax and of intraperitoneal injection. Procedures that may benefit from ultrasound guidance include trigger point injections, nerve blocks, and joint injections.
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Fluoroscopy is frequently used for interventional pain procedures. It is highly effective for visualizing bony structures and observing the spread of radiopaque contrast agents. Live fluoroscopy with contrast agent should be used to minimize the risk of intravascular injection of therapeutic agents. Care should be taken to avoid excessive use of fluoroscopy and to employ appropriate radiation shielding, given the risks of ionizing radiation to the patient and to the health care team members in the fluoroscopy suite.
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Trigeminal Nerve Block
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The two principal indications for trigeminal nerve block are trigeminal neuralgia and intractable facial cancer pain. Depending on the site of pain, these blocks may be performed on the gasserian ganglion itself, on one of the major divisions (ophthalmic, maxillary, or mandibular), or on one of their smaller branches.
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The rootlets of cranial nerve V arise from the brainstem and join one another to form a crescent-shaped sensory (gasserian) ganglion in Meckel’s cave. Most of the ganglion is invested with a dural sleeve. The three subdivisions of the trigeminal nerve arise from the ganglia and exit the cranium separately. (Figure 47-8A).
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Gasserian Ganglion Block
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Fluoroscopic guidance is mandatory for the performance of this procedure (Figure 47-8B). An 8- to 10-cm 22-gauge needle is inserted approximately 3 cm lateral to the angle of the mouth at the level of the upper second molar. The needle is then advanced posteromedially and angled superiorly to bring it into alignment with the pupil in the anterior plane and with the mid-zygomatic arch in the lateral plane. Without entering the mouth, the needle should pass between the mandibular ramus and the maxilla, and lateral to the pterygoid process to enter the cranium through the foramen ovale. After a negative aspiration for cerebrospinal fluid and blood, local anesthetic is injected.
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Blocks of the Ophthalmic Nerve and Its Branches
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In this procedure, to avoid denervation-related keratitis, only the supraorbital branch is blocked in most cases (Figure 47-8C); the ophthalmic division itself is not blocked. The nerve is easily located and blocked with local anesthetic at the supraorbital notch, which is located on the supraorbital ridge above the pupil. The supratrochlear branch can also be blocked with local anesthetic at the superior medial corner of the orbital ridge.
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Blocks of the Maxillary Nerve and Its Branches
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With the patient’s mouth slightly opened, an 8- to 10-cm 22-gauge needle is inserted between the zygomatic arch and the notch of the mandible (Figure 47-8D). After contact with the lateral pterygoid plate at about 4-cm depth (position 1 in figure), the needle is partially withdrawn and angled slightly superiorly and anteriorly to pass into the pterygopalatine fossa (position 2). Local anesthetic is injected once paresthesias are elicited. Both the maxillary nerve and the sphenopalatine (pterygopalatine) ganglia are usually anesthetized by this technique. The sphenopalatine ganglion (and anterior ethmoid nerves) can be anesthetized transmucosally with topical anesthetic applied through the nose; several cotton applicators soaked with local anesthetic (cocaine or lidocaine) are inserted along the medial wall of the nasal cavity into the area of the sphenopalatine recess. The sphenopalatine ganglion blockade may be helpful for patients with chronic nasal pain, cluster headache, or Sluder’s neuralgia.
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The infraorbital branch of cranial nerve V passes through the infraorbital foramen, where it can be blocked with local anesthetic. This foramen is approximately 1 cm below the orbit and is usually located with a needle inserted about 2 cm lateral to the nasal ala and directed superiorly, posteriorly, and slightly laterally.
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Blocks of the Mandibular Nerve and Its Branches
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With the patient’s mouth slightly opened (Figure 47-8E), an 8 to10-cm 22-gauge needle is inserted between the zygomatic arch and the mandibular notch. After contact with the lateral pterygoid plate (position 1 in figure), the needle is partially withdrawn and angled slightly superiorly and posteriorly toward the ear (position 2). Local anesthetic is injected once paresthesias are elicited.
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The lingual and inferior mandibular branches of the mandibular nerve may be blocked intraorally utilizing a 10-cm 22-gauge needle (Figure 47-8F). The patient is asked to open the mouth maximally and the coronoid notch is palpated with the index finger of the nonoperative hand. The needle is then introduced at the same level (approximately 1 cm above the surface of the last molar), medial to the finger but lateral to the pterygomandibular plica (position 1 in figure). It is advanced posteriorly 1.5-2 cm along the medial side of the mandibular ramus, making contact with the bone (position 2). Both nerves are usually blocked following injection of local anesthetic.
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The terminal portion of the inferior alveolar nerve may be blocked as it emerges from the mental foramen at the mid-mandible just beneath the corner of the mouth. Local anesthetic is injected once paresthesias are elicited or the needle is felt to enter the foramen.
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Complications of a gasserian ganglion block include accidental intravascular injection, subarachnoid injection, Horner’s syndrome, and motor block of the muscles of mastication. The potential for serious hemorrhage is greatest for blockade of the maxillary nerve. The facial nerve may be unintentionally blocked during blocks of the mandibular division.
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Blockade of the facial nerve is occasionally indicated to relieve spastic contraction of the facial muscles, to treat herpes zoster involving the facial nerve, and to facilitate certain surgical procedures involving the eye.
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The facial nerve can be blocked where it exits the cranium through the stylomastoid foramen. A small sensory component supplies special sensation (taste) to the anterior two thirds of the tongue and general sensation to the tympanic membrane, the external auditory meatus, soft palate, and part of the pharynx.
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The entry point is just anterior to the mastoid process, beneath the external auditory meatus, and at the midpoint of the mandibular ramus. The nerve is approximately 1-2 cm deep and is blocked with local anesthetic just below the stylomastoid process.
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If the needle is inserted too deeply past the level of the styloid bone, the glossopharyngeal and vagal nerves may also be blocked. Careful aspiration is necessary because of the proximity of the facial nerve to the carotid artery and the internal jugular vein.
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Glossopharyngeal Block
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Glossopharyngeal nerve block may be used for patients with pain due to cancer involving the base of the tongue, the epiglottis, or the palatine tonsils. It can also be used to distinguish glossopharyngeal neuralgia from trigeminal and geniculate neuralgia.
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The nerve exits from the cranium via the jugular foramen medial to the styloid process and courses anteromedially to supply the posterior third of the tongue, pharyngeal muscles, and mucosa. The vagus and spinal accessory nerves also exit the cranium via the jugular foramen and descend alongside the glossopharyngeal nerve in close proximity to the internal jugular vein.
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The block is performed using a 5-cm 22-gauge needle inserted just posterior to the angle of the mandible (Figure 47-9). The nerve is approximately 3-4 cm deep; therefore, use of a nerve stimulator facilitates correct placement of the needle. An alternative approach is from a point over the styloid process, midway between the mastoid process and the angle of the mandible; the nerve is located just anteriorly.
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Complications include dysphagia and vagal blockade resulting in ipsilateral vocal cord paralysis and tachycardia. Block of the accessory nerve and hypoglossal nerves causes ipsilateral paralysis of the trapezius muscle and the tongue, respectively. Careful aspiration is necessary to prevent intravascular injection.
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Occipital Nerve Block
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Occipital nerve block is useful diagnostically and therapeutically in patients with occipital headaches and neuralgias.
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The greater occipital nerve is derived from the dorsal primary rami of the C2 and C3 spinal nerves, whereas the lesser occipital nerve arises from the ventral rami of the same roots.
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The greater occipital nerve is blocked approximately 3 cm lateral to the occipital prominence at the level of the superior nuchal line (Figure 47-10); the nerve is just medial to the occipital artery, which is often palpable. The lesser occipital nerve is blocked 2-3 cm more laterally along the nuchal ridge. Ultrasound guidance may be employed to help identify the nerves and minimize the risk of inadvertent intravenous or intraarterial injection. For patients who have responded well but temporarily to occipital nerve blocks, implantation of an occipital nerve stimulator may provide prolonged relief.
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Rarely, intravascular injections may occur.
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Suprascapular Nerve Block
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This block is useful for painful conditions arising from the shoulder (most commonly arthritis and bursitis).
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The suprascapular nerve is the major sensory nerve of the shoulder joint. It arises from the brachial plexus (C4-C6) and passes over the upper border of the scapula in the suprascapular notch to enter the suprascapular fossa.
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The nerve is blocked at the suprascapular notch, which is located at the junction of the lateral and middle thirds of the superior scapular border (Figure 47-11). Correct placement of the needle is determined by paresthesia, ultrasound, or the use of a nerve stimulator.
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Pneumothorax is possible if the needle is advanced too far anteriorly. Paralysis of the supraspinatus and infraspinatus muscles will result in impaired shoulder abduction.
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Cervical Paravertebral Nerve Blocks
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Cervical paravertebral nerve blocks can be useful diagnostically and therapeutically for patients with cervical disc displacement, cervical foraminal stenosis, or cancer-related pain originating from the cervical spine or shoulder.
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The cervical spinal nerves lie in the sulcus of the transverse process of their respective vertebral levels. As noted earlier in this chapter, unlike thoracic and lumbar nerve roots, those in the cervical spine exit the foramina above the vertebral bodies for which they are named.
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The lateral approach is most commonly used to block C2-C7 (Figure 47-12). Patients are asked to turn the head to the opposite side while in a sitting or supine position. A line is then drawn between the mastoid process and Chassaignac’s tubercle (the tubercle of the C6 transverse process). A series of injections are made with a 5-cm 22-gauge needle along a second parallel line 0.5 cm posterior to the first line. In the case of diagnostic blocks, a smaller injectate volume may be helpful in order to minimize local anesthetic spread to adjacent structures and thereby increase block specificity. Because the transverse process of C2 is usually difficult to palpate, the injection for this level is placed 1.5 cm beneath the mastoid process. The other transverse processes are usually interspaced 1.5 cm apart and are 2.5-3 cm deep. Fluoroscopy is useful in identifying specific vertebral levels during diagnostic blocks. This procedure may also be performed with ultrasound guidance.
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Unintentional intrathecal or epidural anesthesia at this level rapidly causes respiratory paralysis and hypotension. Injection of even small volumes of local anesthetic into the vertebral artery causes unconsciousness and seizures. Other complications include Horner’s syndrome, as well as blockade of the recurrent laryngeal and phrenic nerves.
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Embolic cerebrovascular and spinal cord complications have resulted from injection of particulate steroid with this block. Particulate steroid should not be used with cervical paravertebral nerve blocks because of possible anomalous vertebral artery anatomy in this region.
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Thoracic Paravertebral Nerve Block
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This technique may be used to block the upper thoracic segments, because the scapula interferes with the intercostal technique at these levels. Unlike an intercostal nerve block, a thoracic paravertebral nerve block anesthetizes both the dorsal and ventral rami of spinal nerves. It is therefore useful in patients with pain originating from the thoracic spine, thoracic cage, or abdominal wall, including compression fractures, proximal rib fractures, and acute herpes zoster. This block is also frequently utilized for intraoperative anesthesia and for postoperative pain management in breast surgery.
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Each thoracic nerve root exits from the spinal canal just inferior to the transverse process of its corresponding spinal segment.
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This block may be performed with the patient prone, lateral, or seated position. A 5- to 8-cm 22-gauge spinal needle with an adjustable marker (bead or rubber stopper) is used. With the classic technique, the needle is inserted 4-5 cm lateral to the midline at the spinous process of the level above. The needle is directed anteriorly and medially using a 45° angle with the mid-sagittal plane, and advanced until it contacts the transverse process of the desired level. The needle is then partially withdrawn and redirected to pass just under the transverse process. The adjustable marker on the needle is used to mark the depth of the spinous process; when the needle is subsequently withdrawn and redirected, it should not be advanced more than 2 cm beyond this mark. An alternative technique that may decrease the risk of pneumothorax uses a more medial insertion point and a loss-of-resistance technique very similar to epidural anesthesia. The needle is inserted in a sagittal plane 1.5 cm lateral to the midline at the level of the spinous process above and advanced until it contacts the lateral edge of the lamina of the level to be blocked. It is then withdrawn to a subcutaneous position and reinserted 0.5 cm more laterally but still in a sagittal plane. As the needle is advanced, it engages the superior costotransverse ligament, just lateral to the lamina and inferior to the transverse process. The correct position may be identified by loss of resistance to injection of saline when the needle penetrates the costotransverse ligament. Ultrasound guidance is helpful in performing this block (see Chapter 46).
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The most common complication of paravertebral block is pneumothorax; accidental intrathecal, epidural, and intravascular injections may also occur. Sympathetic blockade and hypotension may be obtained if multiple segments are blocked or a large volume is injected at one level. A chest radiograph is mandatory if the patient exhibits signs or symptoms of pneumothorax.
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Lumbar Paravertebral Nerve Blocks
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Lumbar paravertebral nerve blocks may be useful in evaluating pain due to disorders involving the lumbar spine or spinal nerves.
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The lumbar spinal nerves enter the psoas compartment as soon as they exit through the intervertebral foramina beneath the pedicles and transverse processes. This compartment is formed by the psoas fascia anteriorly, the quadratus lumborum fascia posteriorly, and the vertebral bodies medially.
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The approach to lumbar spinal nerves is essentially the same as for thoracic paravertebral blockade (Figure 47-13). An 8-cm 22-gauge needle is usually used. Radiographic confirmation of the correct level is helpful. For diagnostic blocks, only 2 mL of local anesthetic is injected at any one level, because larger volumes may block more than one level. Larger volumes of local anesthetic are used for therapeutic blocks, or to produce complete somatic and sympathetic block of the lumbar nerves.
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Complications are primarily those of unintentional intrathecal or epidural anesthesia. Patients may experience paresthesias if inadvertent nerve injury occurs during needle placement. Some physicians advocate the use of a blunt-tipped needle to (theoretically) decrease the chance of accidental intraneural injection. Digital subtraction angiography with radiopaque contrast may lessen the risk of intravascular injection of local anesthetic or steroid.
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Cervical, Thoracic, & Lumbar Medial Branch Blocks
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These blocks may be utilized in patients with back pain to assess the contribution of lumbar facet (zygapophyseal) joint disease. Corticosteroids are commonly injected with the local anesthetic when the intraarticular technique is chosen. The cervical, thoracic, or lumbar facet joints may be injected for diagnostic and potentially therapeutic purposes.
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Each facet joint is innervated by the medial branches of the posterior primary division of the spinal nerves above and below the joint (Figure 47-14). Thus, every joint is supplied by two or more adjacent spinal nerves. Each medial branch crosses the upper border of the lower transverse process running in a groove between the root of the transverse process and the superior articular process.
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These blocks are performed under fluoroscopic guidance with the patient in a prone position, or in some cases, the lateral position for cervical procedures. A posterior-anterior view facilitates visualization of the spine for lumbar medial branch blocks. A 10-cm 22-gauge needle is inserted 3-4 cm lateral to the spinous process at the desired level and directed anteriorly toward the junction of the transverse process and the superior articular process to block the medial branch of the posterior division of the spinal nerve (Figures 47-15, 47-16 and 47-17).
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Alternatively, local anesthetic with or without corticosteroid may be directly injected into the facet joint. Positioning the patient prone and using an oblique fluoroscopic view facilitates identification of the joint space. Correct placement of the needle may be confirmed by injecting radiopaque contrast prior to injection of local anesthetic. Total injection volumes should ideally be limited to less than 1 mL in order to prevent rupture of the joint capsule.
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Injection into a dural sleeve results in a subarachnoid block, whereas injection near the spinal nerve root results in sensory and motor block at that level. Because the joint normally has a small volume, larger injections can cause rupture of the joint capsule.
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If a patient achieves improved pain control after a diagnostic block, he or she may be considered for radiofrequency ablation of the medial branch. There is debate about whether a second, confirmatory diagnostic block should be performed prior to radiofrequency ablation. Injection of steroid may be considered before or after radiofrequency ablation to theoretically decrease the chance for post-procedural neuritis.
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Trans-Sacral Nerve Block
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This technique is useful in the diagnosis and treatment of pelvic and perineal pain. In addition, blockade of the S1 spinal root can help define its role in back pain.
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The five paired sacral spinal nerves and one pair of coccygeal nerves descend in the sacral canal. Each nerve then travels through its respective intervertebral foramen. The S5 and coccygeal nerves exit through the sacral hiatus.
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While the patient is prone, the sacral foramina are identified with a needle along a line drawn 1.5 cm medial to the posterior superior iliac spine and 1.5 cm lateral to the ipsilateral sacral cornu (Figure 47-18). Correct positioning requires entry of the needle into the posterior sacral foramen and usually produces paresthesias. The S1 nerve root is usually 1.5 cm above the level of the posterior superior iliac spine along this imaginary line. Blockade of the S5 and coccygeal nerves can be accomplished by injection at the sacral hiatus.
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Complications are rare but include nerve damage and intravascular injection.
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Pudendal nerve block is useful in evaluating patients with perineal somatosensory pain.
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The pudendal nerve arises from S2-S4 and courses between the sacrospinous and the sacrotuberous ligaments to reach the perineum.
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This block is usually performed transperineally with the patient in the lithotomy position (Figure 47-19) although it may be performed via a posterior approach in the prone position. Injection of anesthetic is carried out percutaneously just posterior to the ischial spine at the attachment of the sacrospinous ligament. The ischial spine can be palpated transrectally or transvaginally. Alternatively, this procedure may be performed in the prone position with a 22-gauge needle directed toward the base of the ischial spine. Patients should be advised that they may have numbness of the genitalia for hours after this procedure is performed.
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Potential complications include unintentional sciatic blockade and intravascular injection.
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Sympathetic Nerve Blocks
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Sympathetic blockade can be accomplished by a variety of techniques, including intrathecal, epidural, and paravertebral blocks. Unfortunately, these approaches usually block both somatic and sympathetic fibers. Problems with differential spinal and epidural techniques are discussed below. The following techniques specifically block sympathetic fibers and can be used to define the role of the sympathetic system in a patient’s pain and possibly also provide long-term pain relief. The most common indications for sympathetic nerve blocks include reflex sympathetic dystrophy, visceral pain, acute herpetic neuralgia, postherpetic pain, and peripheral vascular disease. Isolated sympathetic blockade to a region is characterized by loss of sympathetic tone, as evidenced by increased cutaneous blood flow and cutaneous temperature, and by unaltered somatic sensation. Other tests include loss of the skin conductance (sympathogalvanic reflex) and sweat response (ninhydrin, cobalt blue, or starch tests) following a painful stimulus.
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Cervicothoracic (Stellate) Block
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This block is often used for patients with head, neck, arm, and upper chest pain. It is commonly referred to as a stellate block but usually blocks the upper thoracic as well as all cervical ganglia. Injection of larger volumes of anesthetic often extends the block to the T5 ganglia. Stellate blocks may also be used for vasospastic disorders of the upper extremity.
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Sympathetic innervation of the head, neck, and most of the arm is derived from four cervical ganglia, the largest being the stellate ganglion. The latter usually represents a fusion of the lower cervical and first thoracic ganglia. Some sympathetic innervation of the arm (T1) as well as innervation of all of the thoracic viscera derives from the five upper thoracic ganglia. The sympathetic supply to the arm in some persons may also originate from T2-T3 via anatomically distinct nerves (Kuntz’s nerves) that join the brachial plexus high in the axilla. These nerves may be missed by a stellate block but not an axillary block. The point of injection is at the level of the stellate, which lies posterior to the origin of the vertebral artery from the subclavian artery, anterior to the longus colli muscle and the first rib, anterolateral to the prevertebral fascia, and medial to the scalene muscles.
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The paratracheal technique is most commonly used (Figure 47-20), although an oblique or posterior approach may also be taken. With the patient’s head extended, a 4- to 5-cm 22-gauge needle is inserted at the medial edge of the sternocleidomastoid muscle just below the level of the cricoid cartilage at the level of the transverse process of C6 (Chassaignac’s tubercle) or C7 (3-5 cm above the clavicle). The nonoperative hand should be used to retract the muscle together with the carotid sheath prior to needle insertion. The needle is advanced to the transverse process and withdrawn 2-3 mm prior to injection. Aspiration must be carried out in two planes before a 1-mL test dose is used to exclude unintentional intravascular injection into the vertebral or subclavian arteries or subarachnoid injection into a dural sleeve. A total of 5-10 mL of local anesthetic may be injected. Although this procedure is often performed under fluoroscopy, ultrasound may also be used to visualize the anatomy and decrease the risk of inadvertent intravascular injection.
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Correct placement of the needle is usually followed promptly by an increase in the skin temperature of the ipsilateral arm and the onset of Horner’s syndrome. The latter consists of ipsilateral ptosis, meiosis, enophthalmos, nasal congestion, and anhydrosis of the neck and face. This may be considered a side effect of the block rather than a complication.
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In addition to intravascular and subarachnoid injection, other complications of stellate block include hematoma, pneumothorax, epidural anesthesia, brachial plexus block, hoarseness due to blockade of the recurrent laryngeal nerve, and, rarely, osteomyelitis or mediastinitis following esophageal puncture, particularly if a left-sided approach is taken. The posterior approach may have the highest incidence of pneumothorax.
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Thoracic Sympathetic Chain Block
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The thoracic sympathetic ganglia lie just lateral to the vertebral bodies and anterior to the spinal nerve roots, but this block is generally not used because of a significant risk of pneumothorax.
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Splanchnic Nerve Block
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Three groups of splanchnic nerves (greater, lesser, and least) arise from the lower seven thoracic sympathetic ganglia on each side and descend alongside the vertebral bodies to communicate with the celiac ganglia. Although similar to celiac plexus block, the splanchnic nerve block may be preferred because it is less likely to block the lumbar sympathetic chain and because it requires less anesthetic.
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The needle is inserted 6-7 cm from the midline at the lower end of the T11 spinous process, and advanced under fluoroscopic guidance to the anterolateral surface of T12. Ten milliliters of local anesthetic is injected on each side. The needle should maintain contact with the vertebral body at all times to avoid a pneumothorax. Other complications may include hypotension and possible injury to the azygos vein on the right or to the hemiazygos vein and the thoracic duct on the left.
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If a patient’s pain lessens after a splanchnic nerve block, the procedure may be repeated to ensure that this result was not due to placebo effect. In addition, if the patient obtained pain relief from the initial block, he or she may subsequently benefit from radiofrequency ablation of the splanchnic nerves at T11 and T12, with potentially longer duration of analgesia. Performing the procedure on one side initially, and then the other side on a subsequent day, is advised due to the risk of pneumothorax.
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A celiac plexus block is indicated for patients with pain arising from the abdominal viscera, particularly intraabdominal cancers.
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The celiac ganglia vary in number (1-5), form, and position. They are generally clustered at the level of the body of L1, posterior to the vena cava on the right, just lateral to the aorta on the left, and posterior to the pancreas.
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The patient is placed in a prone position and a 15-cm 22-gauge needle is used to inject 15-20 mL of local anesthetic (Figure 47-21). Under fluoroscopic guidance, each needle is inserted 7-8 cm from the midline at the inferior edge of the spinous process of L1. It is advanced under radiographic guidance toward the midline, making an approximately 10-45° angle. The needle passes under the edge of the twelfth rib and should be positioned anterior to the body of L1 in the lateral radiographic view and close to the midline overlying the same vertebral body in the anteroposterior view. When CT guidance is used, the tip of the needle should come to lie anterolateral to the aorta at a level between the celiac and superior mesenteric arteries.
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The celiac plexus block may be performed from multiple approaches including a posterior retrocrural approach, a posterior anterocrural approach, a posterior transaortic approach, and an anterior approach. These blocks may be facilitated with the use of fluoroscopy, CT, or ultrasound guidance.
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The most common complication is postural hypotension, from block of the visceral sympathetic innervation and resultant vasodilation. For this reason, patients should be adequately hydrated intravenously prior to this block. Accidental intravascular injection into the vena cava is more likely to produce a severe systemic reaction than accidental intraaortic injection. Other, less common, complications include pneumothorax, retroperitoneal hemorrhage, injury to the kidneys or pancreas, sexual dysfunction, or, rarely, paraplegia (due to injury to the lumbar artery of Adamkiewicz). Blocking the sympathetic chain may result in relatively unopposed parasympathetic activity that may lead to increased gastrointestinal motility and diarrhea. Back pain is another common side effect of a celiac plexus block.
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Lumbar Sympathetic Block
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Lumbar sympathetic block may be indicated for painful conditions involving the pelvis or the lower extremities, and possibly for some patients with peripheral vascular disease.
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The lumbar sympathetic chain contains three to five ganglia and is a continuation of the thoracic chain. It also supplies sympathetic fibers to the pelvic plexus and ganglia. The lumbar sympathetic chain ganglia are in a more anteromedial position to the vertebral bodies than the thoracic ganglia, and are anterior to the psoas muscle and fascia. The lumbar chain is usually posterior to the vena cava on the right but is just lateral to the aorta on the left.
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A single-needle technique at the L3 level on either side is most commonly employed with the patient either prone or in a lateral position (Figure 47-22). The needle is inserted at the upper edge of the spinous process and is directed above or just lateral to the transverse process of the vertebrae (depending on the distance from the midline). Fluoroscopic guidance with injection of radiopaque contrast prior to local anesthetic injection is often used.
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Complications include intravascular injection into the vena cava, aorta, or lumbar vessels and somatic nerve block of the lumbar plexus. In particular, the genitofemoral nerve may be blocked.
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Superior Hypogastric Plexus Block
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This procedure is indicated for pain that originates from the pelvis and is unresponsive to lumbar or caudal epidural blocks. The hypogastric plexus contains visceral sensory fibers that bypass the lower spinal cord. This block is usually appropriate for patients with cancer of the cervix, uterus, bladder, prostate, or rectum. It may also be effective in some women with chronic noncancer pelvic pain.
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The hypogastric plexus contains not only postganglionic fibers derived from the lumbar sympathetic chain, but also visceral sensory fibers from the cervix, uterus, bladder, prostate, and rectum. The superior hypogastric plexus usually lies just to the left of the midline at the L5 vertebral body and beneath the bifurcation of the aorta. The fibers of this plexus divide into left and right branches and descend to the pelvic organs via the left and right inferior hypogastric and pelvic plexuses. The inferior hypogastric plexus additionally receives preganglionic parasympathetic fibers from the S2-S4 spinal nerve roots.
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The patient is positioned prone, and a 15-cm needle is inserted approximately 7 cm lateral to the L4-L5 spinal interspace. The needle is directed medially and caudally under fluoroscopic guidance so that it passes by the transverse process of L5. In its final position, the needle should lie anterior to the intervertebral disc between L5 and S1 and within 1 cm of the vertebral bodies in the anteroposterior view. Injection of radiopaque contrast confirms correct position of the needle in the retroperitoneal space; 8-10 mL of local anesthetic is then injected. The superior hypogastric plexus block may also be performed using a transdiscal approach, though there is a risk of discitis associated with this procedure.
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Complications include intravascular injection and transient bowel and bladder dysfunction.
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Ganglion impar block is effective for patients with visceral or sympathetically maintained pain in the perineal area.
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The ganglion impar (ganglion of Walther) is the most caudal part of the sympathetic trunks. The two lowest pelvic sympathetic ganglia often fuse forming one ganglion in the midline just anterior to the coccyx.
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The patient may be positioned in the prone, lateral decubitus, or lithotomy position. A 22-gauge needle is advanced through the sacrococcygeal ligament and the rudimentary disc into a position just anterior to the coccyx. This procedure can be facilitated with fluoroscopy or ultrasound. Radiofrequency ablation, or in some cases a neurolytic injection, may provide longer duration of analgesia for this sympathetically mediated pain.
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Intravascular injection and transient bowel or bladder dysfunction are possible. Alternative approaches involve placement of the needle through the anococcygeal ligament, although these may have higher potential to perforate the rectum.
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Intravenous Regional Block
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A Bier block (see Chapter 46) utilizing local anesthetic solution with or without adjuvants can be used to interrupt sympathetic innervation to an extremity. A total volume of 50 mL of 0.5% lidocaine is typically injected, either alone or in combination with clonidine (150 mcg) and in some cases ketorolac (15-30 mg). A tourniquet is placed proximally on the extremity, which is then elevated and exsanguinated using an Esmarch bandage. The tourniquet is inflated to a pressure that is two times the systolic blood pressure, the Esmarch bandage is removed, and the limb is checked to be certain the pulse is absent and there is no evidence of blood flow. The solution is then injected and usually left in place for at least 30 min, after which the tourniquet is released incrementally and the patient is observed for any signs or symptoms of local anesthetic toxicity. Premature release of the tourniquet may result in seizure, hypotension, arrhythmia, edema, diarrhea, and nausea. Intravenous regional sympathetic block is a safe alternative to standard sympathetic blocks in patients with hemostatic defects.
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Epidural steroid injections (Figure 47-23) are used for symptomatic relief of pain associated with nerve root compression (radiculopathy). Pathological studies often demonstrate inflammation following disc herniation. Clinical improvement appears to be correlated with the resolution of nerve root edema. Epidural steroid injections are clearly superior to local anesthetics alone. They are most effective when given within 2 weeks of pain onset but appear to be of little benefit in the absence of neural compression or irritation. Long-term studies have failed to show any persistent benefit after 3 months, and these injections may change the time course of pain relief without changing long-term outcomes.
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The two most commonly used agents are methylprednisolone acetate (40-80 mg) and triamcinolone diacetate (40-80 mg). Dexamethasone is being used with increased frequency due to its smaller particulate size (smaller than an erythrocyte). Intravascular injection of steroid suspension with larger particulate size may lead to embolic complications. The steroid may be injected with diluent (saline) or local anesthetic in volumes of 6-10 mL or 10-20 mL for lumbar and caudal injections, respectively. Simultaneous injection of opioids offers no added benefit and may significantly increase risks. The epidural needle should be cleared of the steroid prior to its withdrawal to prevent formation of a fistula tract or skin discoloration. Injection of local anesthetic along with the steroid can be helpful if the patient has significant muscle spasm, but it is associated with risks of intrathecal, subdural, and intravascular injection. The presenting pain is often transiently intensified following injection, and the local anesthetic provides immediate pain relief until the steroidal antiinflammatory effects take place, usually within 12-48 h.
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Epidural steroid injections may be most effective when the injection is at the site of injury. Only a single injection is given if complete pain relief is achieved. If there is a good but temporary response, a second injection may be given 2-4 weeks later. Larger or more frequent doses increase the risk of adrenal suppression and systemic side effects. Most pain practitioners utilize fluoroscopy for epidural injection and confirm correct placement with injection of radiopaque contrast (Figures 47-24, 47-25 and 47-26). A transforaminal epidural steroid injection may be more effective than the standard interlaminar epidural technique, especially for radicular pain. The needle is directed under fluoroscopic guidance into the foramen of the affected nerve root; contrast is then injected to confirm spread into the epidural space and absence of intravascular injection prior to steroid injection. This technique differs from a selective nerve root block (SNRB) in two important ways; with an SNRB, the needle does not enter the foramen and the injected solution tracks along the nerve but not into the epidural space. The SNRB may be helpful as a diagnostic procedure for the surgeon who is considering a foraminotomy at a particular affected level based upon imaging, clinical presentation, and the results of the SNRB.
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Caudal injection may be used in patients with previous back surgery when scarring and anatomic distortion make lumbar epidural injections more difficult. Unfortunately, migration of the steroid to the site of injury may not be optimal. The use of a catheter to direct the injection within the sacral and epidural canal may improve outcome. However, above the level of S2, there is a risk of thecal perforation with a stylet-guided catheter. Intrathecal steroid injections are not recommended because the ethylene glycol preservative in the suspension has been implicated in arachnoiditis following unintentional subarachnoid injections.
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Radiofrequency Ablation & Cryoneurolysis
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Percutaneous radiofrequency ablation (RFA) relies on the heat produced by current flow from an active electrode that is incorporated at the tip of a special needle. The needle is positioned using fluoroscopic guidance. Electrical stimulation (2 Hz for motor responses, 50 Hz for sensory responses) and impedance measurement via the electrode prior to ablation also help confirm correct electrode positioning. Depending on the location of the block, the heating temperature generated at the electrode is precisely controlled (60-90°C for 1-3 min) to ablate the nerve without causing excessive collateral tissue damage. RFA is commonly used for trigeminal rhizotomy and medial branch (facet) rhizotomy. It has also been used for dorsal root rhizotomy and lumbar sympathectomy. Pain relief is usually limited to 3-12 months due to nerve regeneration after RFA. This may be effective for medial branches of the spinal nerves that innervate facet joints. The lesion from thermal RFA is typically ovoid in shape and dependent upon factors such as the gauge of the needle, the temperature of the needle tip, and the duration of the heating procedure. Cooling the RFA needle with a sterile water system may decrease the charring associated with thermal lesioning and extend the spread of the lesion while heating at lower temperatures. Pulsed radiofrequency at 42°C is also being evaluated for various pain conditions.
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Cryoanalgesia may produce temporary neurolysis for weeks to months by freezing and thawing tissue. The temperature at the tip of a cryoprobe rapidly drops as gas (carbon dioxide or nitrous oxide) at a high pressure is allowed to expand. The probe tip, which can achieve temperatures of -50°C to -70°C, is introduced via a 12- to 16-gauge catheter. Electrical stimulation (2-5 Hz for motor responses and 50-100 Hz for sensory responses) helps confirm correct positioning of the probe. Two or more 2-min cycles of freezing and thawing are usually administered. Cryoanalgesia is most commonly used to achieve long-term blockade of peripheral nerves. It may be particularly useful for post-thoracotomy pain. Patients often have neuropathic pain following thoracotomy or similar surgery. Diagnostic intercostal nerve blocks may be helpful to identify the nerve(s) that may be contributing to chronic thoracic or abdominal pain, and intercostal nerve blocks may also be utilized for longer term analgesia. The principal risks of intercostal nerve blocks are pneumothorax and local anesthetic toxicity. RFA of the intercostal nerves may be helpful as a palliative therapy for intercostal neuralgia, although there is a risk of deafferentation pain after this procedure.
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Neurolytic blocks are indicated for patients with severe, intractable cancer pain in whom more conventional therapy proves inadequate or conventional analgesic modalities are accompanied by unacceptable side effects. The most common chemical neurolytic techniques utilized for cancer patients are celiac plexus, lumbar sympathetic chain, hypogastric plexus, and ganglion impar blocks. Chemical neurolysis may also occasionally be used in patients with refractory benign neuralgia and, rarely, in patients with peripheral vascular disease. These blocks can be associated with considerable morbidity (loss of motor and sensory function), so patients must be selected carefully, and only after thorough consideration of alternative analgesic modalities. Moreover, although the initial result may be excellent, the original pain may recur, or new (deafferentation or central) pain will develop, in a majority of patients within weeks to months.
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Temporary destruction of nerve fibers or ganglia can be accomplished by injection of alcohol or phenol. These neurolytic agents are not selective, affecting visceral, sensory, and motor fibers equally. Ethyl alcohol (50-100%) causes extraction of membrane phospholipids and precipitation of lipoproteins in axons and Schwann cells, whereas phenol (6-12%) appears to coagulate proteins. Alcohol causes severe pain on injection, thus local anesthetic is usually administered first. For peripheral nerve blocks, alcohol may be given undiluted, but for sympathetic blocks in which large volumes are injected, it is given in a 1:1 mixture with bupivacaine. Phenol is usually painless when injected either as an aqueous solution (6-8%) or in glycerol; a 12% phenol solution can be prepared in radiopaque contrast solution.
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Neurolytic Techniques
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Neurolytic celiac plexus or splanchnic nerve blocks may be effective for painful intraabdominal neoplasms, especially pancreatic cancer. Lumbar sympathetic, hypogastric plexus, or ganglion impar neurolytic blocks can be used for pain secondary to pelvic neoplasms. Neurolytic saddle block can provide pain relief for patients with refractory pain from pelvic malignancy; however, bowel and bladder dysfunction should be expected. Neurolytic intercostal blocks can be helpful for patients with painful rib metastases. Additional neurodestructive procedures, such as pituitary adenolysis and cordotomy, may be useful in end-of-life palliative care.
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When considering any neurolytic technique, at least one diagnostic block with a local anesthetic solution alone should be used initially to confirm the pain pathway(s) involved and to assess the potential efficacy of the planned neurolysis. Local anesthetic solution should again be injected immediately prior to the neurolytic agent under fluoroscopic guidance. Following injection of any neurolytic agent, the needle must be cleared with air or saline prior to withdrawal to prevent damage to superficial structures.
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Many clinicians prefer alcohol for celiac plexus block and phenol for lumbar sympathetic block. For subarachnoid neurolytic techniques, very small amounts of neurolytic agent (0.1 mL) are injected. Alcohol is hypobaric, whereas phenol in glycerin is hyperbaric; the patient undergoing subarachnoid neurolysis is carefully positioned so that the solution travels to the appropriate level and is confined to the dorsal horn region following subarachnoid administration.
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Cancer patients frequently receive anticoagulation therapy if they are at elevated risk for venous thromboembolic phenomena. When such a patient has discontinued anticoagulant medication in preparation for a diagnostic local anesthetic block, it may be more practical to obtain consent for a neurolytic procedure in advance and to follow the diagnostic block immediately with chemical neurolysis if the diagnostic procedure has resulted in pain relief.
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Differential Neural Blockade
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Pharmacological or anatomic differential neural blockade has been advocated as a method of distinguishing somatic, sympathetic, and psychogenic pain mechanisms. The procedure is controversial owing to the challenges of interpreting the data and the inability to define exactly which nerve fibers or pathways are blocked. Theoretically, the pharmacological approach relies on the differential sensitivity of nerve fibers to local anesthetics. Preganglionic sympathetic (B) fibers are reported to be most sensitive, closely followed by pain (Aδ) fibers, somatosensory (Aβ) fibers, motor fibers (Aα), and finally C fibers. By using different concentrations of local anesthetic, it may be possible to selectively block certain types of fibers while preserving the function of others. The challenge is that the critical concentration needed to block sympathetic fibers can vary considerably between patients, and conduction block by local anesthetics is dependent not only on fiber size but also on the duration of contact and frequency of impulses conducted. Many clinicians have therefore abandoned the use of pharmacological differential neural blocks in favor of anatomic differential blockade.
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Stellate ganglion blocks can be used to selectively block sympathetic fibers to the head, neck, and arm. Celiac plexus, hypogastric plexus, and lumbar paravertebral sympathetic blocks can be used for sympathetic blocks of the abdomen, pelvis, and leg, respectively. Selective nerve root, intercostal, cervical plexus, brachial plexus, or lumbosacral plexus blocks may be used for somatic nerve blockade.
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Differential epidural blocks may be used for thoracic pain when the techniques for sympathetic blockade carry a significant risk of pneumothorax (Table 47-16). After each epidural injection, the patient is evaluated for pain relief, signs of sympathetic blockade (a decrease in blood pressure), sensation to pinprick and light touch, and motor function. If the pain disappears after the saline injection, the patient either has psychogenic pain (usually a profound long-lasting effect) or is displaying a placebo effect (usually short lasting). If pain relief coincides with isolated signs of sympathetic blockade, it is likely mediated by sympathetic fibers. If pain relief only follows somatosensory blockade, it is likely mediated by somatic fibers. Lastly, if the pain persists even after signs of motor blockade, the pain is either central (supraspinal) or psychogenic.
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The differential epidural block carries the risk of any neuraxial block, and the possibility of hypotension and blocking cardiac accelerator fibers at T1-T4. The level should not extend above the T5 dermatome due to these risks. Following catheter insertion, injections should be administered with the patient in a monitored setting for the rest of this procedure.
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Although differential epidural blockade has limitations, it may be helpful to identify primarily centralized pain when a patient continues to have a significant level of pain despite multilevel dermatomal blockade over the painful region. It is unlikely that a subsequent nerve block would help to treat the painful condition.
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When it is thought that a patient may have abdominal pain from the anterior abdominal wall, a transversus abdominis plane (TAP) block may be performed using ultrasound guidance. This may offer potential short- or long-term relief and can be considered as an alternative to differential epidural blockade. If no relief is obtained, the pain may have a visceral origin or a central cause. Visceral pain may best respond to a celiac or splanchnic nerve block and possibly to subsequent splanchnic RFA. Patients with pain that is primarily of a central origin may respond to multidisciplinary therapy, including counseling and biofeedback training.
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Electrical stimulation of the nervous system can produce analgesia in patients with acute and chronic pain. Current may be applied transcutaneously, epidurally, or by electrodes implanted into the central nervous system.
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Transcutaneous Electrical Nerve Stimulation
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Transcutaneous electrical nerve stimulation (TENS) is thought to produce analgesia by stimulating large afferent fibers. It may have a role for patients with mild to moderate acute pain and those with chronic low back pain, arthritis, and neuropathic pain. The gate theory of pain processing suggests that the afferent input from large epicritic fibers competes with that from the smaller pain fibers. An alternative theory proposes that at high rates of stimulation, TENS causes conduction block in small afferent pain fibers. With conventional TENS, electrodes are applied to the same dermatome as the pain and are stimulated periodically by direct current from a generator (usually for 30 min several times a day). A current of 10-30 mA with a pulse width of 50-80 μs is applied at a frequency of 80-100 Hz. Some patients whose pain is refractory to conventional TENS respond to low-frequency TENS (acupuncture-like TENS), which employs stimuli with a pulse width greater than 200 μs at frequencies less than 10 Hz (for 5-15 min). Unlike conventional TENS, low-frequency stimulation is at least partly reversed by naloxone, suggesting a role for endogenous opioids. This technique is also called dorsal column stimulation because it was thought to produce analgesia by directly stimulating large Aβ fibers in the dorsal columns of the spinal cord. Proposed mechanisms include activation of descending modulating systems and inhibition of sympathetic outflow.
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Spinal Cord Stimulation
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Spinal cord stimulation (SCS) may be effective for neuropathic pain; accepted indications include sympathetically mediated pain, spinal cord lesions with localized segmental pain, phantom limb pain, ischemic lower extremity pain due to peripheral vascular disease, adhesive arachnoiditis, peripheral neuropathies, post-thoracotomy pain, intercostal neuralgia, postherpetic neuralgia, angina, visceral abdominal pain, and visceral pelvic pain. Patients with persisting pain after back surgery, which is typically a mixed nociceptive-neuropathic disorder, also appear to benefit from SCS.
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Temporary electrodes are initially placed in the posterior epidural space and connected to an external generator to evaluate efficacy in a 5- to 7-day trial (Figures 47-27 and 47-28). The trial may be extended, particularly if it allows a patient, such as one with CRPS, to tolerate more aggressive physical therapy. If a favorable response is obtained, a fully implantable system is inserted. Unfortunately, the effectiveness of the technique decreases with time in some patients. Complications include infection, lead migration, and lead breakage.
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Peripheral Nerve Stimulation
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Peripheral nerve stimulation (PNS) differs from SCS in that leads are placed in close anatomic proximity to an injured peripheral nerve. The leads may be placed percutaneously, with or without ultrasound guidance, or surgically under direct vision of the nerve. Occipital nerve stimulators are one form of peripheral nerve stimulator that may be helpful in treating occipital neuralgia and migraine headache (Figure 47-29).
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Deep Brain Stimulation
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Deep brain stimulation (DBS) is used for intractable cancer pain and for intractable nonmalignant neuropathic pain. Electrodes are implanted stereotactically into the periaqueductal and periventricular gray areas for nociceptive pain, usually in patients with cancer or chronic low back pain. For neuropathic pain, the electrodes are frequently implanted into the ventral posterolateral and ventral posteromedial thalamic nuclei. DBS may also be helpful for patients with movement disorders, headache, and neuropsychiatric disorders. The most serious complications are intracranial hemorrhage and infection.
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Multidisciplinary Treatment
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Psychological Interventions
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Psychological techniques, including cognitive therapy, behavioral therapy, biofeedback, relaxation techniques, and hypnosis, are most effective when employed by psychologists or psychiatrists. Cognitive interventions are based on the assumption that a patient’s attitude toward pain can influence the perception of pain. Maladaptive attitudes contribute to suffering and disability. The patient is taught skills for coping with pain either individually or in group therapy. The most common techniques include attention diversion and imagery. Behavioral (operant) therapy is based on the premise that behavior in patients with chronic pain is determined by consequences of the behavior. Positive reinforcers (such as attention from a spouse) tend to enable or intensify the pain, whereas negative reinforcers reduce pain. The therapist’s role is to guide behavior modification with the aid of family members and medical providers in order to nurture negative reinforcers and minimize positive reinforcers.
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Relaxation techniques teach the patient to alter the arousal response and the increase in sympathetic tone associated with pain. The most commonly employed technique is a progressive muscle relaxation exercise. Biofeedback and hypnosis are closely related interventions. All forms of biofeedback are based on the principle that patients can be taught to control involuntary physiological parameters. Once proficient in the technique, the patient may be able induce a relaxation response and more effectively apply coping skills to control physiological factors (eg, muscle tension) that worsen pain. The most commonly utilized physiological parameters in biofeedback are muscle tension (electromyographic biofeedback) and temperature (thermal biofeedback). The effectiveness of hypnosis varies considerably among individuals. Hypnotic techniques teach patients to alter pain perception by having them focus on other sensations, localize the pain to another site, and dissociate themselves from a painful experience through imagery. Patients with chronic headaches and musculoskeletal disorders benefit most from these relaxation techniques.
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Heat and cold can provide pain relief by alleviating muscle spasm. In addition, heat decreases joint stiffness and increases blood flow, and cold vasoconstricts and can reduce tissue edema. The analgesic action of heat and cold may at least partially be explained by the gate theory of pain processing.
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Superficial heating modalities include conductive (hot packs, paraffin baths, fluidotherapy), convective (hydrotherapy), and radiant (infrared) techniques. Techniques for application of deep heat include ultrasound as well as shortwave and microwave diathermy. These modalities are more effective for pain involving deep joints and muscles. Cold is most effective for pain associated with acute injuries and edema. When applied selectively, cold can also relieve muscle spasm. Application may take the form of cold packs, ice massage, or vapocoolant sprays (ethyl chloride or fluoromethane).
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Exercise should be part of any rehabilitation program for chronic pain. A graded exercise program prevents joint stiffness, muscle atrophy, and contractures, all of which can contribute to the patient’s pain and functional disabilities. McKenzie exercises are particularly helpful for patients with lumbar disc displacement. Patients may state that physical therapy has not helped in the past. The efficacy of previous physical therapy techniques should be assessed, and the appropriateness of current physical therapy sessions and of the home exercise program should also be evaluated. By facilitating increased range of motion and providing constant resistance, aquatherapy may be particularly helpful for patients who may not be able to tolerate other forms of therapy.
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Acupuncture can be a useful adjunct for patients with chronic pain, particularly that associated with chronic musculoskeletal disorders and headaches. The technique involves insertion of needles into discrete anatomically defined points, called
meridians. Stimulation of the needle after insertion takes the form of twirling or of application of a mild electrical current. Insertion points appear to be unrelated to the conventional anatomy of the nervous system. Although the scientific literature concerning the mechanism of action and role of acupuncture in pain management is controversial, some studies suggest that acupuncture stimulates the release of endogenous opioids, as its effects can be antagonized by
naloxone.