17 Complications of Regional Anesthesia in Chronic Pain Therapy

(1)

17 Complications of Regional Anesthesia in Chronic Pain Therapy

Philip W.H. Peng and Vincent W.S. Chan

301 Interest in interventional pain management is on the rise, as indicated by an increased enrollment into the anesthesiology pain fellowship programs in North America.¹ The prevalence of treatment-related complications has also increased, as suggested in a recent Closed Claims study.² In this chapter, we discuss sympathetic, visceral, and somatic blocks frequently used in the management of chronic pain. To understand how complications arise, it is necessary to review the anatomy and techniques of the blocks, which can be used for diagnostic or therapeutic purposes. It is also important to understand some of the unique drugs used in this setting (e.g., neurolytic agents and corticosteroids). In general, procedure-related damage can result from needle insertion, misplacement or unanticipated spread of the drug, drug toxicity, injection of the wrong substance, or from an idiosyncratic reaction. Postblock physiologic changes may also add to complications.

Sympathetic Blocks

Sympathetic blockade techniques are frequently used in the diagnosis and treatment of sympathetically mediated pain syndromes, limb ischemia or hypoperfusion, and visceral pain from cancer or nonmalignant conditions.³ Diagnostic blocks with local anesthetic alone are often performed as a precursor to either a series of blocks or neurolytic block using phenol or ethanol.

Stellate Ganglion Block

The stellate ganglion is formed by the fusion of the inferior cervical and ﬁ rst thoracic sympathetic ganglia lying on the longus colli muscle, anterior to the seventh cervical transverse process and neck of the ﬁ rst rib. The most common approach to the stellate ganglion is an anterior paratracheal approach at the level of the cricoid cartilage (C6).

The needle is directed to the prominent anterior tubercle of C6 (Chassaignac’s tubercle) followed by a large-volume local anesthetic injection (up to 20 mL). The sympathetic outﬂ ow to the head and neck region (cervical trunk) can be blocked independently of the ﬁ bers to the upper limb.⁴ Thus, development of Horner’s syndrome does not guarantee successful sympathetic blockade of the upper limb.

Also described are an anterior C7 paratracheal approach and a posterior T2 paravertebral approach.⁵ The posterior approach aims to interrupt sympathetic outﬂ ow

(2)

to the upper extremity with less chance of Horner’s syndrome. Thus, it may be indicated for neurolytic blockade when long-term side effects are undesirable.

Needle Trauma

Structures that lie close to the path of needle insertion are at theoretical, if not actual, risk of injury. Moore⁶ documented puncture of pharynx, trachea, and esophagus.

Pneumothorax is another recognized risk, especially with the anterior C7 approach, as the dome of the pleura may extend 2.5 cm above the level of the ﬁ rst rib, especially on the right side. The risk of pneumothorax is increased further in tall, thin persons.

The incidence of pneumothorax is up to 4% with the posterior approach, which shares many of the risks of the thoracic paravertebral sympathetic block.

Intravascular Injection

The vessel most at risk for intravascular injection during stellate ganglion block is the vertebral artery. At the level of C7, the vertebral artery lies anterior to the stellate ganglion, before it swings posterior to enter the foramen transversarium of the sixth cervical transverse process. Thus, the anterior C7 paratracheal approach has a greater risk of vertebral artery puncture. Kozody et al.⁷ have shown that as little as 2.5 mg of bupivacaine (a test dose) can cause major central nervous system (CNS) effects when accidentally injected into the vertebral artery. A smaller 1-mL test dose is recommended. Intravertebral artery local anesthetic injection may produce dizziness, nausea, light-headedness, and hypotension with low dose and can result in coma, convulsion, and respiratory depression in high dose.⁸ These are attributed to the direct effects of local anesthetic on medullary and pontine centers. The duration and nature of the toxic effects depend on the dose injected and global and regional cerebral blood ﬂ ow, as well as the precise neurovascular anatomy. Local anesthetic-induced neurologic symptoms, which appear after a low-dose injection, are often short-lived (minutes).

Accidental injection of air into the vertebral artery, with subsequent cerebral air embolism was reported by Adelman.⁹ This complication represents two errors, not just one. Other vascular structures at risk are the carotid and jugular vessels, which lie lateral to the needle path, but there are no recent reports of puncture.

Intraspinal Injection

Nerve roots of the brachial plexus exiting from intervertebral foramen may have an accompanying dural cuff. The vertebral canal and its contents lie posteromedial to the stellate ganglion. Thus, dural puncture may occur,¹⁰ either as a result of needle placement too medial or injection into a lateral extension of the perineural dural cuff of the cervical somatic nerve root. Intrathecal injection of local anesthetic will produce a high spinal block, characterized by loss of consciousness, high motor block, hypotension, and apnea. This serious complication necessitates ventilatory and hemodynamic support until it wears off. Subdural injection has also been reported.¹¹

Wulf and Maier,¹² in a survey of approximately 45,000 stellate ganglion blocks performed in Germany, reported six subarachnoid blocks and three high epidural injections. Most important of all, care should be taken to avoid inadvertent injection of neurolytic agents into the epidural, subdural, or subarachnoid spaces, because this may lead to long-term neurologic deﬁ cit.

Anomalous Spread of Drug

Even when the drug is injected into the correct anatomic plane, anomalous spread may cause complications. Both bilateral recurrent laryngeal nerve palsy and contra- lateral Horner’s syndrome have been reported.¹³ Bilateral block causes unopposed vocal cord adduction and airway obstruction. Local anesthetic spread posteriorly and

(3)

anterolaterally can produce brachial plexus blockade and phrenic nerve block, respectively. Because of the possibility of somatic spread, it is necessary to check for normal sensory and motor function in the blocked limb when evaluating the success of the sympathetic block.

Drug Effects

Extensive blockade of the cardiac sympathetic nerves has been reported following a properly performed stellate ganglion block. This resulted in bradycardia, secondary to unopposed vagal tone.¹⁴ Schlack et al.¹⁵ demonstrated in a canine model that left stellate ganglion blockade caused impairment of left ventricular function. The mechanism was asymmetric cardiac contraction and asynchrony, caused by loss of sympathetic tone in the anteroapical segment of the left ventricle, supplied by the left sympathetic chain. Although it is difﬁ cult to extrapolate these animal data to humans, who may have different patterns of myocardial innervation, the authors suggest that it may remain a risk in patients with already compromised cardiac function. Data to conﬁ rm this are lacking.

One case of migraine has been reported following a stellate ganglion block, presumably caused by an idiosyncratic reaction and a loss of unilateral sympathetic tone in the cerebral vasculature.¹⁶ Absorption of correctly injected local anesthetics to toxic levels is unlikely in stellate ganglion blockade, because the mass of drug used is usually within the therapeutic range.¹⁷ There have been no recent reports of injection of the wrong drug, but it remains a theoretical possibility.

Thoracic and Lumbar Sympathetic Blockade

The sympathetic chain lies in the paravertebral region, receiving ﬁ bers from somatic nerve roots via the rami communicantes. In the thoracic region, it lies adjacent to the neck of the ribs, relatively close to the somatic nerve roots and the parietal pleura.

Pneumothorax is deﬁ nitely a possible complication. For this reason, the transcutane- ous approach to the thoracic sympathetic chain without radiologic imaging support is not frequently performed. Long-lasting thoracic sympathectomy is usually achieved by surgical ablation, either by thoracotomy or, more recently, thoracoscopy.

In the lumbar region, the sympathetic chain and its ganglia lie on the anterolateral border of the vertebral bodies, separated from the somatic nerve roots by the psoas muscle and fascia. The ganglia are found in variable locations but most consistently found at the L3 level.¹⁸ The classical paramedian technique requires the insertion of a needle 5–6 cm from the posterior midline with the patient in the prone position. The needle passes through the paravertebral muscles, “walks off” the transverse process of L2, L3, or L4, and passes through the psoas muscle and fascia to reach the lumbar sympathetic chain in the anterolateral aspect of the vertebra.

The other approach is more lateral, using ﬂ uoroscopy to determine the needle insertion point so that it will pass lateral to the transverse process en route to the anterolateral border of the L2, L3, or L4 vertebrae. The volume of local anesthetic injection also varies, from high volume (e.g., 20 mL) at a single level to low volume at multiple levels. Although no study to date has demonstrated superiority of one approach over the other, the single-level, high-volume technique seems to be most popular.¹⁹

Intraspinal and Intravascular Injection

The vertebral column and the spinal canal lie posteromedial to the sympathetic chain.

Injection of local anesthetic in the spinal canal is rare, but theoretically possible.

Intraspinal injection (intrathecal, epidural, or subdural) and postdural puncture headache (PDPH) can follow puncture of either an extended dural cuff or the intraspinal dura.^20,21 Intravascular injection is a possible complication, because both the aorta and inferior vena cava lie anterior to the sympathetic chain. Puncture of these structures

(4)

is rarely reported, but it occurs in clinical setting. The vertebral venous plexus is another vascular structure at risk, because it is close to the path of the needle. The risk of intravascular injection into either a perivertebral vein or a major vessel should be minimized by appropriate use of ﬂ uoroscopy and contrast medium before the injection of local anesthetic or neurolytic agents.

Needle Trauma

Conﬁ rmation of needle position with ﬂ uoroscopy is necessary when performing neurolytic blocks of the lumbar sympathetic ganglia. The risks of “blind” technique are needle trauma to the kidney, ureter, and bowel. In a cadaver study, three of 80 “blind”

needle attempts resulted in needle impalement in grossly osteoporotic vertebral bodies or the hilum of the kidney.²² These incidents would have been prevented by the use of ﬂ uoroscopy.

Drug Effects

Complications can occur from the drug used in the sympatholysis, from either local anesthetics or neurolytic agents. Signifi cant sympathetic blockade and postural hypotension may occur, as part of physiologic response to a drug. Another possible undesirable effect is sexual dysfunction in male patients, although this may also be caused by vascular insuffi ciency, an indication for lumbar sympathetic block in the fi rst place.

There remains a possibility that sympathetic blockade of a limb where there is critical fi xed stenosis of the arterial supply to one region may vasodilate only the normal vasculature. This will give rise to a “steal” syndrome – deterioration of perfusion to the ischemic area, if there is a fi xed infl ow.

The most frequent complication associated with lumbar chemical sympathectomy is genitofemoral neuralgia.²³ The genitofemoral nerve arises from the lumbar plexus at the ﬁ rst lumbar segmental level and passes on the ventral surface of the psoas muscle. It emerges from the anterior aspect to supply the groin and upper thigh. The incidence varies between 4% and 15% and most cases are transient, lasting less than 6 weeks.²⁴

Ureteric injury is uncommon but can happen following chemical sympathectomy.²⁵ Whether injury is related to needle trauma or ureterolysis from the neurolytic agents is unclear. Most case reports claimed ﬂ uoroscopic conﬁ rmation of needle location and delayed presentation of urologic symptoms, suggesting that injury is more likely related to the neurolytic agent. This highlights the importance of limiting the amount of neurolytic agents applied.

Intravenous Regional Sympathetic Block

The technique of intravenous sympathetic blockade has become widespread for treatment of sympathetically mediated pain in the upper limb. The technique is essentially one of perfusion of the isolated limb with a sympatholytic solution. After an interval of 20–30 minutes, when the drug can be assumed to have become ﬁ xed to the tissues, the tourniquet is deﬂ ated. The block is repeated, usually weekly for three to six times (see Chapter 13).

Sympatholytic agents used for intravenous regional sympathetic block are guanethidine (not available for this use in the United States), bretylium, reserpine, phen- tolamine, and ketanserin. Guanethidine is one group of drugs that block reuptake of noradrenaline in sympathetic nerve endings for up to 3 days, thus depleting the stores. It should not be used in patients on monoamine oxidase inhibitors for this reason, because there is an initial release of amine from the stores. Guanethidine is usually used in a dose of 10–20 mg in up to 40 mL of saline or dilute local anesthetic for upper limb. The dose and the volume are usually higher for the lower limb. A recent review on the use of this block in patients with peripheral neuropathic pain

(5)

and complex regional pain syndromes suggests this block is not an effective analgesic compared with control (normal saline).²⁶

Drug Effects

Despite the relative simplicity of the technique, there is a risk of unwanted systemic absorption if the drug bypasses the inﬂ ated tourniquet or after it is released. Transient decrease in blood pressure on tourniquet release is common,²⁷ although Sharpe et al.²⁸ reported prolonged hypotension (80 mm Hg for 1 week) after repeated blocks.

Autonomic denervation caused by drug accumulation may be responsible.

Other adverse events following cuff deﬂ ation were transient apnea and syncope during intravenous regional anesthesia using guanethidine and lidocaine.²⁹ Whether this neurologic event was attributable to hypotension or toxic drug reaction is unclear.

Celiac Plexus Block

The celiac plexus innervates the upper abdominal viscera, including pancreas, diaphragm, liver, spleen, stomach, small bowel, ascending and proximal transverse colon, adrenal glands, kidneys, abdominal aorta, and mesentery. It contains preganglionic splanchnic afferent, postganglionic sympathetic ﬁ bers, and parasympathetic ﬁ bers.

Celiac plexus blockade may therefore be indicated in chronic or cancer pain involving these organs – pancreas and stomach being most common.

The greater (T5-10), lesser (T10-11), and least (T12) splanchnic nerves form the preganglionic sympathetic supply for the celiac ganglia. These nerves lie on the thoracic paravertebral border, pierce the diaphragmatic crura, and form the plexus lying on the anterior and lateral aspects of the abdominal aorta, between the origins of the celiac arterial axis and the renal arteries. The celiac ganglia number between one and ﬁ ve and may be up to 4.5 cm in diameter.

Four techniques of blocking the splanchnic nerve and celiac plexus are frequently used. The fi rst is the retrocrural splanchnic nerve block technique. The needles, one on each side, are placed posteriorly and paravertebrally below the twelfth rib and advanced mediad to make contact with the L1 vertebral body. With this approach, the aim is to position the needle tip close to the splanchnic nerves behind the aorta and the diaphragm. A modifi cation of this classical retrocrural technique is to direct the needle more cephalad at the level of the anterolateral margin of T12 vertebra. The theoretical advantage of this modifi cation is to block the visceral sympathetic pathway more effectively with a smaller amount of neurolytic solution.

The second approach is the transcrural technique³⁰ to block the celiac plexus proper by positioning the needles (one on each side) farther anterior and through the diaphragmatic crura. Under radiologic guidance, the drug is deposited anterior and caudal to the crura and posterior to the aorta. A smaller volume of drug is needed, thus minimizing the risk of somatic block. The third approach is the transaortic approach developed by Ischia³¹ using a single needle from the left side of the back. The advantages of this technique are a single needle insertion and a smaller dose requirement of local anesthetic or neurolytic agent, and so a lower risk of retrocrural somatic spread. However, there is a slightly higher risk of hematoma formation.

The fourth approach is a percutaneous anterior approach. Fine needles guided by ultrasound may be used.³² Visceral or vascular perforation can occur, but the sequelae of perforation may be minimized by antibiotic coverage and avoidance of the technique in “coagulopathic” patients. Celiac plexus block can also be performed under direct vision at the end of laparotomy. Alternatively, endoscopic ultrasound–guided injection is a safe and cost-effective approach.³³ With an ultrasound transducer mounted in front of the viewing lens of the endoscope, the aorta and celiac artery can be easily identiﬁ ed as reference landmarks before injection.

(6)

Hypotension

Because of the sympathetic blockade of splanchnic vasculature, the most common complication of celiac plexus blockade is hypotension. Without adequate prehydration or vasopressor drugs, this may occur in 30%–60% of patients. In a metaanalysis of neurolytic celiac plexus blocks, Eisenberg et al.³⁴ reported 10 studies covering 571 patients, of whom 217 (38%) had hypotension. Splanchnic vasodilatation and visceral blood pooling contribute to orthostatic hypotension. For this reason, it is recommended that blood pressure and the electrocardiogram be monitored for 2 hours after a block. After block, the patients should remain supine or in the lateral position for at least 1 hour, or until they can stand unaided. A degree of postural hypotension may last up to 2 days.

Diarrhea

Unopposed parasympathetic activity following celiac plexus block can lead to gastro- intestinal hypermotility.³⁵ Additionally, after a successful celiac plexus block, the patient will need smaller doses of opiate analgesics. The incidence of transient diarrhea may be up to 44%,³⁴ lasting a few days, but rarely persisting longer. When diarrhea occurs in the presence of preexisting dehydration and pooling of blood in the splanchnic circulation, life-threatening hypovolemia may appear if massive intestinal ﬂ uid loss is not replaced. Somatostatin has been suggested as therapy in this situation, and octreotide may have a role in treatment of persistent diarrhea.

Needle Trauma

Needle puncture and drug injection into the aorta, vena cava, renal vessels, and various viscera have been reported.³⁶ The anatomy may be distorted by tumor or other mass in the retroperitoneum or abdomen. One expects the risk of hematoma formation to be highest with Ischia’s transaortic approach. Aortic puncture is more likely with needle placement on the left side than on the right side. A large retroperitoneal hematoma after vascular puncture may cause hypovolemia and must be differentiated from hypotension caused by splanchnic vasodilatation. Limiting the size of needle and ensuring normal patient coagulation status will reduce the risk of bleeding.

Aortic dissection after formation of an infected pseudoaneurysm has been reported after celiac plexus block,³⁷ possibly related to the effect of neurolytic agent on the aortic wall. Kaplan et al.³⁸ reported fatal aortic dissection, which extended to the superior mesenteric and hepatic artery, resulting in extensive liver and bowel infarction.

Unintentional injection between vertebrae producing an incidental discogram was reported by Wilson.³⁹ Pneumothorax is another theoretical complication, even though the point of needle insertion is below the twelfth rib. Chylothorax has been reported in association with tumor and after puncture of the cisterna chyli during celiac plexus block.⁴⁰ The cisterna chyli classically lies anterior to the ﬁ rst two lumbar vertebrae to the right of the aorta, but this is variable. The transdiaphragmatic movement of the retroperitoneal lymph collection is via the lymphatics. Retroperitoneal ﬁ brosis after multiple blocks has been reported.⁴¹

Infection

Because of the proximity of the needle path to the bowel, especially with the anterior and endoscopic ultrasound approach, infection is a concern. Retroperitoneal abscess has been reported.^42,43

Neurologic and Neurovascular Sequelae

The most serious complications of celiac plexus block are neurologic.⁴⁴ There are several mechanisms. Drug misplacement and anomalous or excessive retrocrural

(7)

spread can affect epidural and lumbar somatic nerve roots. Direct accidental intrathecal injection can also occur. Unintended intrathecal injection of neurolytic agents will lead to permanent paraplegia. Permanent and extensive autonomic blockade may cause male sexual dysfunction.

The arterial supply to the spinal cord may be damaged during celiac plexus block.

The anatomy of the blood supply is variable, and the major radicular artery of Adam- kiewicz may arise from T7 to L4. In 80% of cases it lies on the left. It enters via a single intervertebral foramen to supply the anterior spinal artery of the lower two- thirds of the cord. Damage to this artery (either mechanical by a needle or chemical by neurolytic drug) may lead to paraplegia. Although radiologically guided techniques minimize the incidence of direct intravascular injection, neurolytic drugs deposited perivascularly may alter arterial reactivity and cause vasospasm. This has been demonstrated in isolated canine lumbar arteries in vitro.⁴⁵

There are several reports of paraplegia following neurolytic celiac plexus block using phenol⁴⁶ or alcohol.⁴⁷ Injury to artery of Adamkiewicz caused by compression, spasm, or both can lead to anterior spinal artery syndrome.⁴⁸ There is a possibility that using only a right-sided approach might lessen the incidence, but it might also diminish the effectiveness. A few reports of transient and reversible paraplegia have also been reported after alcohol celiac plexus block.⁴⁹

The incidence of paraplegia is difﬁ cult to estimate, because the total number of blocks performed is not known. It may lie between 0.1% and 0.5%, based on a metaanalysis by Eisenberg et al.³⁴ Davies⁵⁰ surveyed complications of all blocks done in a 5-year period (1986–1990) in England and found four patients with paraplegia among 2730 blocks. Alcohol (50%–99%) was injected under ﬂ uoroscopic control in all four patients. This gives a major neurologic complication rate of 1 in 683 (0.15%). In a review by Fugere and Lewis,⁵¹ the overall incidence of all complications (as detailed above plus pain) was approximately 1.8% in 20 series covering 30 years.

In addition to arterial complications, superior mesenteric venous thrombosis has also been reported.⁵²

Drug Effects

Phenol-induced cardiotoxicity may account for a report of cardiac arrest in a patient undergoing intraoperative splanchnic nerve block during laparotomy.⁵³ Ventricular ﬁ brillation occurred 3 minutes after injection of 30 mL of 6.66% phenol, after negative aspiration under direct vision. The authors cite other reports of cardiac toxicity of phenol, mostly arising from transdermal absorption in dermatologic and plastic surgical practice, where much higher doses are used.

Systemic effects have been reported as a result of absorption of a large volume of alcohol administered for retrocrural celiac plexus block. Measured serum ethanol concentration was up to 39 mg/dL after an injection of 25 mL of 50% ethanol bilater- ally⁵⁴ and 29 mg/dL after 15 mL of 99.5% ethanol.⁵⁵ Although this will not cause any serious impairment, and is below the legally defi ned limit for intoxication, the authors noted that all patients reported a feeling of mild euphoria. However, toxic alcohol levels may appear in patients who have a genetic defi ciency of aldehyde dehydroge- nase, which is relatively common in the Japanese population. There is also a possibility of interaction with drugs such as disulfi ram or metronidazole, although this has not so far been reported.

In summary, the retrocrural technique has the lowest risk of visceral or vascular puncture, but a higher risk of somatic nerve block because of a larger volume of drug.

Transcrural injection requires smaller volumes but has a slightly increased risk of perforation of vital visceral structures. Transaortic celiac plexus block, a single-needle technique, uses the least amount of drug but most likely causes vascular damage and hematoma formation even with a ﬁ ne needle.

(8)

Other Visceral Nerve Blocks

The superior hypogastric nerve and the ganglion impar are two other sites amenable to blockade for chronic or cancer pain of the lower abdominal or pelvic organs.⁵⁶ The superior hypogastric plexus is found on the anterior aspect of the sacrum, in the midline. Approach to the superior hypogastric plexus is percutaneous, from a point between the sacral ala and the interspace between the L4 and L5. The needle passes anteromedially and caudad, lateral to the sacral nerve roots and medial to the iliac vessels. The ganglion impar lies on the concavity of the sacrum, and is blocked per- cutaneously using a specially bent needle inserted toward the sacrococcygeal junction.

There are no recent reports of complications from block of this nerve.

Facet Joint Block

The lumbar facet (zygapophyseal) joint has long been considered by some to be a signiﬁ cant source of low back pain⁵⁷ whereas cervical facet joint disease is linked to chronic neck pain. The facet or zygapophyseal joints are true synovial joints with considerable sensory innervation and overlap. The medial branch of the posterior ramus supplies the lower pole of one facet joint and the upper pole of the adjoining facet joint.

A diagnostic facet joint injection or a medial branch block may be considered for patients with back pain. Both blocks are believed to have equal diagnostic sensitivity.⁵⁸ Real-time ﬂ uoroscopic guidance is recommended to ensure accurate needle placement because being off target by a few millimeters can result in aberrant drug spread to intervertebral neural foramen and the epidural space, yielding false-positive results of pain relief.⁵⁹ Injection of contrast material (0.5 mL) can enhance accuracy, and local anesthetic injection of 1–1.5 mL (small volume) will decrease the risk of spread to the epidural space or somatic nerves. In the neck, the vertebral artery lies just lateral to the facet joint; thus intravascular injection or damage is a theoretical risk, but so far it has not been reported.

Medial branch block is an easier procedure to perform, also under X-ray control, and is indicated in patients with severe arthritis and narrowed or obliterated joint space. In the neck, the medial branch is farther from the vertebral artery than the facet joint itself.

Increased Pain

Transient increased pain is the most common side effect (2%–20%) which may last from 6 weeks to 8 months.⁶⁰

Intraspinal Injection

Spinal anesthesia following attempted lumbar facet block has been reported.⁶¹ These cases may be attributable to erroneous needle placement, possibly through a nerve root dura cuff.

Thomson et al.⁶² reported chemical meningism after attempted facet joint block with local anesthetic and steroids, and this was presumably caused by inadvertent intrathecal injection, because there are very few reports of meningism associated with epidural injection of steroids.

Other Complications

Paraspinal abscess formation and septic joint arthritis have been reported following facet joint injection.^63,64 Excessive local anesthetic injection and spread to the somatic roots can cause ipsilateral weakness, although we have found no recent reports of this obvious complication. This may be caused by excessive anterior needle placement, or excess volume causing joint rupture. It should be remembered that the maximum volume of the facet joint is 1.5 mL.

(9)

Radiofrequency Techniques

Radiofrequency neurotomy interrupts nociceptive pathways by applying heat (60˚–

75˚C) from the tip of an electrode to denervate nerves. This technique is used for treatment of trigeminal neuralgia, dorsal rhizotomy, and dorsal root entry zone inter- ruption for deafferentation syndromes.⁶⁵ Radiofrequency procedures can also be used for facet joint denervation in the lumbar and cervical regions. The complications are essentially those caused by needle trauma, needle misplacement, and the low-level heat injury to the nerve. Postblock pain is common in the ﬁ rst 2 weeks after radiofrequency treatment. Cutaneous numbness and dysesthesia is also common but usually resolves in 3 weeks.⁶⁵

Epidural Blockade

The epidural space may be approached in the cervical, thoracic, lumbar, or sacral regions (via sacral hiatus). The most frequently injected agents are steroids and dilute local anesthetics, although opioid has been used in some circumstances.^19,66 The main indication for epidural steroid injection is relief of radicular pain.^67,68 The transforaminal approach to the epidural space has become popular in recent years because it has proven clinical efﬁ cacy over conventional techniques.⁶⁹ In the lumbar spine, the needle is aimed at the superior and ventral quadrant of the neural foramen and in cervical spine, the posterior half of the foramen abutting the anterior surface of superior articular process.⁷⁰ The major advantage of this approach is drug delivery directly to the site of nerve root impingement, as opposed to only a fraction of the injected dose reaching target with the conventional interlaminar approach.⁷¹

Complications of Epidural Steroid Administration

Although epidural steroid injection is considered to be safe, life-threatening complications have occurred. This is a major cause of malpractice claims related to chronic pain management in North America.^2,72 Complications speciﬁ c to steroid injection relate to local or systemic drug effects. Mechanical and traumatic complications can also occur and they are the same as with any epidural injection and are discussed elsewhere (Chapter 10). Speciﬁ c complications that are discussed include drug neurotoxicity, arachnoiditis, infection, systemic effects of steroids and opioids, and serious neurologic complications related to the transforaminal approach.

Arachnoiditis

Arachnoiditis following intentional subarachnoid injection of methylprednisolone acetate can happen. This is documented in a comprehensive review by Abram and O’Connor⁷³ covering 65 published series and 18 case reports in 6947 patients who received one or more epidural steroid injections and 368 patients who received one or more subarachnoid steroid injections. There were no reports of arachnoiditis after epidural injection of steroids when intrathecal injection was excluded. One of the components of the vehicle, polyethylene glycol, has been implicated as the cause of neurotoxicity. Benzon et al.⁷⁴ found that nerve conduction was affected by polyethylene glycol at concentrations much higher (seven times) than clinical relevant concentrations. Even at higher concentrations, the conduction defects were reversible. It should be noted that in clinical practice, the solution is always diluted further with either saline or local anesthetic.

Infectious Sequelae

The risks of neuraxial infection are present when faulty aseptic technique or bacteremia is present, as for any spinal injection (see Chapter 7). In theory, the

(10)

immunosuppressive effects of steroids may increase this risk. Epidural abscess following epidural steroid injection have been reported.^75,76 The patients affected were usually diabetic and the most common bacteria cultured was Staphylococcus aureus, a likely skin contaminant. However, a recent report described an intradural abscess resulting from epidural steroid injections in a young immunocompetent patient.⁷⁷ The culture grew Aspergillus fumigatus. Dougherty and Fraser⁷⁸ reported bacterial meningitis in two patients. These two cases seem to have been caused by dural puncture and not transdural bacterial spread. Cooper and Sharpe⁷⁹ reported a case of S. aureus meningitis after repeated epidural steroid injections at weekly intervals.

It would seem that, despite the theoretical increased risk of infection, clinical reports do not indicate that there is any greater incidence associated with epidural steroids than with local anesthetic agents alone, provided the same precautions and contraindications are noted. Even allowing for underreporting, the incidence just from published series and reports appears to be less than 0.01%. Diabetes seems to pre- dispose patients to this complication.

Systemic Side Effects of Steroid

Suppression of adrenal cortical response has been reported after oral, nasal, inhaled, and parenteral as well as epidural steroid administration. Cushingoid side effects, including ﬂ uid retention, electrolyte imbalance, and fat redistribution, have been reported after epidural steroid injections. Stambough et al.⁸⁰ reported a case of hyper- corticism after two injections a week apart totaling 160 mg of methylprednisolone acetate, whereas Tuel et al.⁸¹ reported one case following a single cervical epidural administration of 60 mg methylprednisolone acetate. In both cases, return of normal clinical and biochemical functions took weeks to months. Knight and Burnell⁸² had reported three occurrences of clinical symptoms consistent with Cushing’s syndrome after multiple epidural injections when methylprednisolone acetate, 200 mg, was exceeded, in a series of injections over less than 2 weeks. There was no laboratory conﬁ rmation.

Iatrogenically induced steroid myopathy (proximal limb) was reported by Boonen et al.⁸³ after epidural triamcinolone diacetate 60 mg. Biochemical adrenal suppression lasted 12 weeks. This case probably represents one tail of a distribution of sus- ceptibility to systemic effect against dosage of steroid given. Maillefert et al.⁸⁴ demonstrated biochemical adrenal suppression in a group of nine patients for up to 21 days after a single epidural injection of dexamethasone acetate, 15 mg. Clinical signs and symptoms were absent. Kay et al.⁸⁵ investigated the effect on the hypotha- lamic-pituitary-adrenal axis of a series of three epidural injections of methylprednisolone acetate 80 mg, at weekly intervals. They also investigated the suppressive effects of concomitant sedation with midazolam, an imidazo-benzodiazepine, a class of drugs known to cause adrenal suppression. Of their 14 patients, ﬁ ve had a sub- normal plasma cortisol response to injections of synthetic adrenocorticotropic hormone 1 month after the ﬁ nal epidural injection, but all returned to normal by 3 months. The adrenal suppressive effect of midazolam lasted less than 15 minutes.

Signiﬁ cant adrenal suppression was detected in the weeks between the injections although there was no clinical abnormality in any patient. Jacobs et al.⁸⁶ suggested that exogenous steroid replacement should be considered for patients having surgery who have had epidural steroids between 1 and 3 months earlier, although the authors were unable to specify predictive factors associated with occurrence or duration of adrenal suppression.

Animal work by Gorski et al.⁸⁷ demonstrated failure of adrenal response after experimental hypoglycemia in beagle dogs. The study group of 12 dogs received bupivacaine plus triamcinolone, 2 mg/kg epidurally, and showed no increase in plasma cortisol in response to insulin-induced hypoglycemic stress for 4 weeks. The control group all showed the expected increase.

(11)

Although there is no consensus for the frequency or dose of steroid administration to prevent systemic side effects, it is prudent not to repeat injections within a 4-week interval and to limit to a maximum of three epidural steroid injections in 6 months based on human and animal data. A recent survey showed that the above clinical guideline was being followed.¹⁹

Systemic Side Effects of Epidural Opioid

The addition of epidural morphine to steroid may further relieve low back pain⁸⁸ but the associated beneﬁ ts vary.^89,90 Most of these early studies added 8 mg of epidural morphine to the steroid. However, life-threatening ventilatory depression was noted in 3 of 14 patients who received an admixture of steroid and morphine (8 mg).⁹¹ Although lower-dose epidural opioid (e.g., morphine 5 mg) has been used, the effect produces analgesia for up to 24 hours.⁹² The common side effects are pruritus (57%–90%), nausea and vomiting (40%–64%), and urinary retention (20%–43%).^89–92

Recent surveys show that 2%–10% of anesthesiologists in North America add opioid to epidural steroids.^19,66 It is important to realize that epidural opioids not only have no proven long-term beneﬁ ts, but death or brain death has been cited in a recent Closed Claims study when injected with epidural steroid.² Although the cause–effect relationship cannot be established, clinicians must carefully weigh the limited beneﬁ t of epidural opioid against potential serious risks.

Severe Neurologic Complication Associated with Transforaminal Injections

Although no major complications were reported in two large case series of more than 1000 transforaminal steroid injections,^93,94 severe neurologic complications appeared in subsequent reports.⁹⁵ Following cervical transforaminal injections, a fatal anterior spinal artery syndrome,⁹⁶ massive cerebellar infarct,⁹⁷ and bilateral complete cortical blindness⁹⁸ have been reported. Transforaminal injections at lumbar or sacral nerve roots have also resulted in severe paraparesis or paraplegia in four patients.^99,100 Most worrisome is that most of these incidents happened despite ﬂ uoroscopic or computed tomography (CT) scan guidance and a presumed “uneventful” injection.

Vascular injury has been implicated as magnetic resonance imaging (MRI) showed spinal cord infarct in these cases. The blood supply to the spinal cord comes from a single anterior spinal artery and two posterior spinal arteries. At each vertebral level, radicular arteries from the aorta travel along with the segmental nerve roots into the neural foramen and supply the corresponding nerve roots. Some of these radicular branches contribute to the perfusion of the anterior spinal cord by joining the anterior spinal artery. The most important radicular artery supplying the lumbar region is the artery of Adamkiewicz (anatomic location discussed earlier in this chapter). In the cervical level, the important contributing radicular artery originates between C3 and C8. Needle trauma to one of the radicular arteries is the likely mechanism of spinal cord injury. Alternatively, the anterior spinal cord circulation can be compromised by a steroid embolus when the preparation is injected intravascularly by accident.¹⁰¹ Tiso et al.⁹⁷ found that both triamcinolone acetonide (Kenalog-40; Bristol-Myers Squibb, Princeton, NJ) and methylprednisolone acetate (Depo-medrol; Pharmacia & Upjohn, Kalamazoo, MI) preparations contain large particles capable of occluding metarteri- oles and arterioles.

The rate of unintentional intravascular injection using the transforaminal approach is estimated to be 11%.⁹⁴ Measures taken to prevent intravascular injection include real-time ﬂ uoroscopic guidance and avoidance of needle movement before and during injection. It is important to note that the sensitivity of a positive blood aspirate in detecting intravascular injections is only 45%.

(12)

Other reactions

Various minor complications have been reported in different case series (Table 17-1).^102–114 Other complications reported in case reports are delayed allergic reaction to an epidural injection of triamcinolone and lidocaine,¹¹⁵ persistent hiccup presumably caused by systemic effect of steroid,¹¹⁶ vision loss secondary to retinal hemor- rhage,¹¹⁷ cervical epidural and subdural hematoma,^118,119 and direct spinal cord injury from needle trauma.¹²⁰

In summary, epidural steroid injection is a safe procedure. However, severe and life-threatening complications have been one of the major causes of Closed Claims in North America because of the frequent use of this procedure. Physicians should be cognizant of the systemic effect of the steroid and limit the amount of steroid used and the number of injections per year. Transforaminal injections are gaining popular- ity but serious neurologic complications can occur. To avoid inadvertent intravascular injection, real-time ﬂ uoroscopy is recommended.

Neural Ablative Procedures

Nerve destruction is reserved mainly as a last resort for patients with debilitating pain related to cancer¹²¹ and occasionally, noncancer conditions (e.g., postherpetic neuralgia¹²² and bone graft donor site¹²³) that is refractory to conventional treatments. Neu- rolysis of peripheral nerves (e.g., sciatic, obturator nerves) has also been applied to relieve muscle spasticity following hemiplegic stroke.¹²⁴ Because neural ablative procedures are seldom practiced, few clinical studies have documented their relative clinical effectiveness, leaving the practice of these procedures rather empirical. Neu- rolysis can be achieved in a number of ways: chemically by neurolytic agents such as alcohol and phenol, by radiofrequency coagulation, cryoprobe, and surgery. For the purpose of this discussion, we will focus on complications associated with chemical neurolysis performed by regional anesthetic procedures.

Table 17-1. Complications and side effects of epidural steroid injection (interlaminar and caudal approach): aggregate data from published series

Injection type No. reported Complications or side effects No. (%)

Cervical epidural 1,788* Neck stiffness,¹⁰² pain¹⁰³ 40 (2.2)

injections Facial ﬂ ushing^102,103 24 (1.3)

Headache¹⁰³ 16 (0.9)

Nausea/vomiting¹⁰² 10 (0.6)

Hypotension (including vagal)^103,104 9 (0.5)

Dural tap^102–104 7 (0.4)

Other (fever, insomnia¹⁰³) 7 (0.4)

Cervical subtotal 123 (6.9)

Headache^105–107 45 (0.34)

Dural tap^108,109 35 (0.26)

Lumbar, thoracic, and 13,233* Hypotension (including vagal)^107,110 17 (0.13) caudal epidural Systemic steroid effects^111,112 6 (0.05)

injections Facial ﬂ ushing¹⁰⁷ 6 (0.05)

Other (fever,¹¹³ nausea, bloody tap,¹¹¹ 26 (0.20)

DVT,¹⁰⁶ insomnia,¹⁰⁷ increased

back/leg pain¹⁰⁷)

Lumbar, thoracic, and 125 (0.94)

caudal subtotal

Total 15,021* All of the above 248 (1.65)

*The total number referred to the number of injections in the case series reported in references 73 (review), 102–111, and 114. A number of case series reported no side effects or complications and the references would not be shown in the table.

(13)

Neurologic complications of chemical neurolysis are drug related and vary according to the site of injection – peripherally on a peripheral nerve and centrally in the epidural or subarachnoid space. Rarely, nonneurologic complications, e.g., broncho- spasm secondary to accidental intrabronchial or intrapulmonary injection of phenol during an intercostal nerve block, occur.¹²⁵ Because neurologic complications are potentially devastating, it is important to select patients appropriately and include only those with limited life expectancy (no more than 6–12 months). The patient and family must have a clear understanding and realistic expectations before neurolytic procedures. Herein, we will highlight the use of peripheral and central neurolysis to treat malignant somatic pain. Neurolytic blocks for visceral and sympathetically mediated pain have been discussed earlier.

Neuropathic Effects of Neurolytic Agents

Neurolytic agents are applied to section a nerve and disrupt its transmission chemically rather than surgically. Agents frequently used are phenol, alcohol, and glycerol.

Less frequently used ones are ammonium sulfate, hypertonic saline, chlorocresol, and butyl aminobenzoate (Butamben). Phenol is usually prepared as an aqueous 5%–7%

solution or as a concentrated 10%–12% solution in glycerin. Alcohol is used most often as a 95% solution. Because of the nature of the vehicle solution, phenol in glycerin is hyperbaric whereas alcohol is hypobaric; this is an important consideration when performing central neurolysis.

The neuropathic effect of alcohol and phenol is nonselective. When applied to neural tissues, phenol coagulates proteins and injures perineural blood vessels, causing neural ischemia; ethyl alcohol extracts from neural membrane cholesterol, phospho- lipid, and cerebroside and causes precipitation of lipoproteins and mucoproteins.

There is no proof that small unmyelinated C ﬁ bers transmitting nociception are more vulnerable to neurolytic destruction than larger A beta sensory ﬁ bers for thermal and mechanical sensation.

Neurologic Complications

Neurolytic agents destroy sensory, sympathetic, and motor nerve fi bers indiscrimi- nately, especially when used in high concentrations and large volumes. To lower the risk of neurologic defi cit, needle placement must be accurate, aided by nerve stimula- tor or radiologic guidance. It is wise to fi rst perform a prognostic local anesthetic block in the same target area before neurolysis. This prognostic block allows the patient and physician to assess the resultant pain relief and the extent of potential damage. Neu- rolytic agents also destroy extraneural structures. Before needle withdrawal, fl ushing of the needle with saline or air is recommended to avoid skin slough and muscle necrosis.

Motor Paresis

Before a neurolytic agent is applied to peripheral mixed nerves supplying the upper or lower limb, patients must clearly understand that destruction of motor ﬁ bers can cause or increase limb weakness. For this reason, neurolysis is ideally reserved for patients with some degree of limb weakness. To preserve residual function, a dilute 3% phenol solution has been used successfully in neurolytic brachial plexus block to alleviate arm pain from lung malignancy.¹²⁶ However, analgesia is short-lived with this approach. Another way to limit harm is lesioning more selectively and peripherally at the target site. For example, Kaplan et al.¹²⁷ performed a selective paravertebral C5-6 nerve root block, and Patt and Millard¹²⁸ performed suprascapular block to treat malignant upper arm pain. The same risk-limiting measures apply when neurolytic block is performed in the lumbosacral plexus for lower extremity pain. On the contrary, although intercostal neurolysis to treat thoracic and abdominal wall pain can impair intercostal muscle function, the damage usually is of little physiologic

(14)

consequence. However, proximal epidural spread has resulted in paraplegia following phenol intercostal neurolysis.¹²⁹

Central neurolysis performed in the epidural or subarachnoid space can also result in postblock motor paresis.¹³⁰ Well-executed, central neurolysis produces neural ablation more selectively, because of greater separation of motor and sensory nerve roots at the spinal cord site of origin. The goal, therefore, is to execute a chemical dorsal rhizotomy (sensory) without ventral rhizotomy (motor).¹²¹ If poorly executed, a cervical and lumbosacral central neurolysis can result in upper and lower limb paresis, respectively. Although rare, quadriplegia caused by anterior spinal artery syndrome has been reported following cervical intrathecal phenol injection.¹³¹

Subarachnoid phenol injection can cause motor paresis, in addition to sensory, bowel, and bladder dysfunction, as a result of posterior spinal artery thrombosis and spinal cord infarction.¹³² Phenol, 8%–12%, and ethanol, 3%–6%, were shown to induce sustained contraction in isolated canine lumbar segmental arteries.⁴⁵ Both anterior and posterior spinal syndromes can occur, presumably secondary to vasospasm and/or thrombosis.

Again, one must limit risk by following some important principles. Strict selection criteria should apply to limit central neurolysis to patients with limited life expectancy and whose pain is localized to 2 or 3 dermatomes. First, one must appropriately pick the target of lesioning. For example, malignant pain of soft tissue is treated by targeting speciﬁ c dermatomes (Figure 17-1), but bony pain in the same area must be treated

F^IGURE 17-1. A side view of the dermatomes (A) and an anterior view of the sclerotomes indicated by the different styles of shading (B). (Reprinted from Haymaker W, Woodhall B.

Peripheral Nerve Injuries. Philadelphia: WB Saunders; 1945:20, 41, with permission from Elsevier.)

C2

C3 C4

C4 C5

C6 C7

C5 L2L3

L3

L5

L2

L3 L4

L4

L5

L5 S1

S1

R.L.O.

S2

C8&

T1 S1

S1

C7 C7

C7 C6

C6 C5

C6

CC7 8 C6

C7_C8

C5

T2

T2 T1 T1

3 4

109 11 12 L1

L2

L3

L5 L4

L5 S1

MAN

FREDI S1

S 2 L3

L2 S4

S3

S2 S3

5 76 8

A B

(15)

differently, by targeting the responsible sclerotomes, not dermatomes. Second, one must place the neurolytic agent as close to the targeted dorsal root as possible. It is important to recognize that the level at which a particular nerve root leaves the spinal cord is generally higher than the corresponding vertebral body. For example, L3 nerve root leaves the spinal cord at the level of T11-12 vertebral body. Thus, when doing a neurolysis of the L3 root, injection should be made at the T11-12 interspace and not L3 (Figure 17-2).

When performing subarachnoid neurolysis, patient positioning is crucial in order to limit inadvertent drug diffusion to the ventral root. Positioning varies according to the choice of neurolytic agent. If hypobaric alcohol is used, the pain site should be positioned uppermost; the opposite is the case when hyperbaric phenol in glycerin is used.¹³³ Furthermore, to target the dorsal root speciﬁ cally, the patient should be positioned at a 45-degree angle anteriorly when using hypobaric solution but should be angled posteriorly when a hyperbaric solution is used. Also, the patient should remain in this position for at least 30–45 minutes after injection, to limit spread elsewhere.

FIGURE 17-2. The alignment of spinal segments with vertebrae. The bodies and spinous processes of the vertebrae are indicated by Roman numerals, the spinal segments and their respective nerves by Arabic. Note the location where the spinal nerves exit through intervertebral foramina in relationship to their respective vertebral bodies. (Reprinted from Haymaker W, Woodhall B. Peripheral Nerve Injuries. Phila- delphia: WB Saunders; 1945:24, with permission from Elsevier.)

C1

I I

II II

III III

IV IV

V V

VI VI

VII VII

TI TI

II II

III III

IV IV

V V

VI VI

VII VII

VIII VIII

IX IX

X X

XI XI

XII XII

LI

II

III

IV

V V

2

2 3 4 5 6 7 8

3 4 5 6 7 8 9 10 11 12

L1

2

3

4

5

S1 2 3 4 5 Coc.1

MAN FREDI

T1 C1

2 3 4 5 6 7 8 T1 2 3 4 5 6 7 8

9 10

11 12 L1

2 3 4 5

S1 2 3 4 5

(16)

Similar to peripheral neurolysis, it is always advisable to ﬁ rst perform a local anesthetic prognostic block to determine adequacy of analgesia, the extent of motor blockade, and paresthesia. One should remember that local anesthetic is not as hypobaric as alcohol, so the resultant block area may be somewhat different. During injection, dose fractionation using 0.1-mL aliquots of alcohol should be used to improve accuracy. If several dermatomal levels are to be blocked, separate subarachnoid injections should be made at each level. One must remember that alcohol does not diffuse well in cerebrospinal ﬂ uid (CSF), and injecting a large volume of alcohol at a single spinal level does not reliably block neighboring levels but increases the risk of motor paresis.

When epidural neurolysis is performed, complications can be minimized if an indwelling catheter is used, so that repeated injections can be given in small incre- ments over several days. Before neurolysis, catheter position should be checked with local anesthetic (not more than 5 mL) to document correct spread of drug and correct catheter tip position in relation to dermatomal pain site. Dosing of neurolytic should be slow. For example, no more than 0.2 mL of alcohol is injected as a bolus and 3–5 mL is injected slowly over 20–30 minutes. Also, one must look for reports of tingling and numbness in nontarget areas (e.g., when doing a midthoracic neurolysis, paresthesia in the ﬁ fth ﬁ nger or anterior thigh is indicative that spreading has gone to nontargeted T2 and L2-3 dermatomes. Neurolytic injection must be stopped right away.)¹³⁴

Loss of Bladder and Bowel Control

Destruction of the S2-4 parasympathetic ﬁ bers supplying the bladder, rectum, and colon can lead to urinary and fecal incontinence, respectively. Central neurolytic block performed in the lumbosacral region poses the greatest risk, although deﬁ cit following thoracic injection has also been reported.¹³⁵ Voiding is less likely to be affected after peripheral neurolysis even when performed in the sacral nerves.¹³⁶ So far, there is only one report of bladder atony after an S3 S4 alcohol block.¹³⁷ To limit risk, it is advisable to do preneurolysis local anesthetic prognostic blocks followed by urodynamic study, perform block under radiologic guidance, and limit injection volume (e.g., 1-mL aliquots at each sacral foramen).

Postblock Pain

Reactive neuritis, neuroma formation, and deafferentation pain are causes of post- neurolytic block pain in the denervated area after an initial period of pain relief.

Painful paresthesia and neuritis develop in 2%–28% of patients after peripheral neurolysis with phenol or alcohol.¹³⁸ Raj¹³⁹ suggested that this may be the result of incom- plete lesioning and pointed out that when phenol intercostal nerve block was executed with precision under direct vision, neither neuritis pain nor deafferentation pain occurred.¹⁴⁰ Many believed that alcohol is more likely to cause neuritis than phenol, but this is unproven.

Pain, in the form of mechanical hypersensitivity, can occur after peripheral neurolysis. This can be attributable to spontaneous ﬁ ring of neuromas that were formed by sprouting of injured axons. Deafferentation pain can also appear as a new form of neuropathic pain. Dysesthesia and hyperalgesia may appear in an area of anesthesia, resembling the anesthesia dolorosa seen in gasserian ganglion neurolysis for trigeminal neuralgia. Thus, neurolysis should be limited to patients with short life expectancy.

Implantable Catheters and Drug Delivery System

Implantable catheters are placed in the epidural^141,142 or subarachnoid (intrathecal)¹⁴³ space for long-term delivery of analgesics for treatment of debilitating pain from malignancy^144–146 and nonmalignant^147–149 conditions. Intrathecal analgesia may be

(17)

preferred over the epidural route because of lower analgesic consumption, fewer drug reﬁ lls, and fewer mechanical problems.^142,150 Additionally, subarachnoid infusion of baclofen¹⁵¹ is sometimes used to treat lower limb spasticity from multiple sclerosis or quadriplegia.

There are three types of intraspinal drug delivery systems.¹⁵² Implantable catheters can be connected to: 1) an internalized subcutaneous programmable pump (e.g., Synchromed Infusion Pump, Medtronic Inc.),¹⁵³ 2) a subcutaneous port (e.g., the Port- a-Cath port system, Pharmacia-Deltec, Inc.), or 3) an externalized delivery system (e.g., Algoline catheter, Medtronic Inc.). The indwelling end of the catheter in the neuraxial space is sutured in place before it is tunneled subcutaneously from the back to the front. Complications of implantable catheter and drug delivery systems are either mechanical or drug related.^154–156 The safety of the externalized delivery system has notably improved in recent years through a change from bolus administration to continuous infusions and modiﬁ cation of line-insertion techniques.¹⁵⁷ Data from lit- erature surveys are summarized in Tables 17-2 and 17-3 giving the incidence of various complications.^158–179

Infection

Postimplantation infection is mostly localized but can become systemic. The risk of infection is higher in immunocompromised patients who have had radiation, chemo- therapy, or chronic systemic (human immunodeﬁ ciency virus) or cutaneous infection.

In patients with stomas (e.g., gastrostomy, enterostomy, or nephrostomy), it is important to direct the path of catheter away from these stoma sites, to avoid potential infection. Frequent change of bacterial ﬁ lters can result in a higher incidence of catheter hub colonization.¹⁸⁰

Localized infection such as an abscess can be formed anywhere along the implanted catheter. It can be superfi cial at the catheter exit site or deep in the subcutaneous pocket housing the access port and internalized pump, along the catheter tract, and in the epidural space. Superfi cial infection often produces purulent exudate at the catheter entry site or localized skin infl ammation. A wound or pocket infection often presents as infl ammatory skin changes overlying the infected area. Fever and leuko- cytosis may not appear in immunocompromised patients. Needle aspirate from local seroma or wound hematoma showing white blood cells and positive Gram stain confi rms the diagnosis.

Epidural or intrathecal space infection and abscess encapsulation¹⁸¹ are often mani- fested in the following manner: pain during injection (not previously present), retro- grade fl ow of infusate and pooling of infused fl uid in the paravertebral region, and decreased analgesia despite increased dose of analgesics. Spinal epidural abscess can also manifest as back pain, radicular signs, and spinal cord compression.¹⁷¹ Common pathogens are skin fl ora contaminants S. aureus and S. epidermidis; less common ones are Escherichia coli, Pseudomonas, Candida albicans, and Mycobacterium organ- isms. A localized infection can track along the catheter until it reaches the epidural space. Otherwise, the epidural space is infected through hematogenous spread or through contamination of the analgesic injectate. Diagnosis is confi rmed by getting an epidural/subarachnoid aspirate sample for Gram stain and culture as well as a MRI or CT scan to look for abscess. Once detected, both infectious disease and neurosur- gery consultants must be involved in patient care.

In the case of an exteriorized catheter, exit site infection can be prevented by regular site cleaning with hydrogen peroxide and chlorhexidine. The catheter and exit site should be protected (e.g., by a minibag) when showering. Bathing in a hot tub is to be avoided. The catheter must always be handled by aseptic technique, and patient and patient’s family are instructed to look for signs of inﬂ ammation. If an infection occurs, treatments are daily cleaning with chlorhexidine and topical or oral antibiot- ics. Complete resolution is expected without catheter removal.