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Intraspinal drug delivery for chronic pain and spasticity: anatomic and physiologic considerations
Seminars in Pain Medicine Vol. 1 No. 4 2003
Intraspinal Drug Delivery for Chronic Pain and Spasticity: Anatomic and Physiologic Considerations SAMI MOUFAWAD, MD and NAGY A. MEKHAIL, MD, PhD
ABSTRACT The intraspinal approach for controlling pain and spasticity is a safe alternative for patients who failed other less invasive modalities. It is rapidly gaining popularity as a valuable tool for this subset of patients. The safety and availability of implantable devices has helped expand the use of this route. The success of this alternative treatment is highly dependent on the physician’s skills and knowledge of the functional anatomy of the spinal cord, its coverings and its supporting structures. Key words: spinal cord, functional anatomy, physiology.
skull through the foramen magnum) to the conus medullaris. The spinal cord has two enlarged areas: in the cervical area and in the lumbosacral segment. In these areas, there is a concentration of cell bodies leading to nerves to and from the upper and lower limbs and the organs in the body cavities. The enlarged areas are the result of the volume required to accommodate these cell bodies. The thoracic segment is relatively slender compared with the other two segments, because the cell bodies supplementing the nerves to the trunk are not as numerous as those supplying the limbs. A clinical implication of these two enlargements is noted when the epidural space is approached: When advancing a catheter or a percutaneous electrode array dorsally, the tip or the catheter or electrode tend to migrate laterally to the gutter containing the dorsal nerve roots, and the operator must apply caution when steering the tip to keep it on the desired track. The conus medullaris ends at the L1-L2 interspace in an adult spine. In the fetus, the spinal cord fills the
Introduction Although the oral route is the preferred method for pain control, the intraspinal drug delivery approach is emerging as a valid alternative for patients who are unable to obtain adequate pain control using simpler methods or those who have intractable side effects. With better understanding of the mechanism of pain signal transmission, modulation, and perception, and with advances in pump technology, intraspinal infusion is becoming the state of the art in managing difficult and complicated pain problems. In addition to proper patient selection, good technique, based on sound knowledge of the anatomy and physiology of the spinal cord and its protective coverings, is the foundation of successful therapeutic intraspinal drug delivery. Such interventions should be tailored to each patient based on a good understanding of the pathology in question. When well applied and appropriately monitored, the intraspinal route of administration is very effective and associated with minimal side effects. Therefore, it is of utmost importance to start with basic discussion of the anatomy and physiology of the spinal cord.
From the Department of Pain Management, The Cleveland Clinic Foundation, Cleveland, OH. Address reprint requests to Nagy A. Mekhail, MD, PhD, Department of Pain Management, The Cleveland Clinic Foundation, 9500 Euclid Avenue, C25, Cleveland, OH 44195. E-mail: [email protected] © 2004 Elsevier Inc. All rights reserved. 1537-5897/04/0104-0007/$30.00/0 doi:10.1016/j.spmd.2004.02.005
Anatomy of the Spinal Cord The spinal cord is the part of the central nervous system extending from the brain stem (exiting the
234
Anatomy and Physiology
vertebral canal. Upon development into adulthood, the bony and ligamentous structures of the spine develop faster than the nervous system, which results in a spinal canal that is longer than the spinal cord. This also explains the downward orientation of the spinal roots, leaving the spinal cord and heading to the corresponding neuroforamina. This downward orientation of the spinal roots is more obvious at the lumbar and sacral regions compared with the cervical and thoracic regions. The conus medullaris is anchored by the filum terminale that is formed by connective tissue and does not contain neural elements. The filum is covered by the pia matter and extends with the cauda equina inside the spinal canal in the subarachnoid space and attaches to the lower end of the spinal canal at the level of the coccyx. The cauda equina (“horse tail”) is the collection of paired nerve roots traveling in the lower end of the spinal canal. The individual nerves are attached to the spinal cord cephalad, and to the corresponding neuroforamen caudad. Functionally, the spinal cord plays a role in connecting the brain to the nerve roots and the peripheral nervous system. It also houses reflex circuits at multiple levels, which play a role in controlling different body functions to include a critical role in the regulation of pain perception, signal transmission, and muscle tone. The spinal cord segmental circuitry modifies the signals transmitted in both directions. The spinal cord is formed by the nerve fibers, cell bodies, and supporting structures. Clusters of cell bodies form nuclei at multiple levels of the spinal cord. The fibers serve as a connection between these nuclei and also transmit signals from the periphery to the central nervous system (CNS) and vice versa. The gross anatomy of the spinal cord is composed mainly of gray and white matter where the gray is mainly central in the form of the letter “H.” This is mainly where the nuclei and cell bodies are located. The gray matter is surrounded by white matter (it is white due to the myelin sheaths covering the nerve fibers running throughout the area). In the center of the spinal cord is a small diameter canal called the ependymal canal. In the embryo the spinal cord develops as a plate that folds and closes to form a tube, the ependymal canal is the rudimentary lumen of that tube. This tube is blind distally and communicates with the fourth ventricle proximally. It does not have any clinical indication except that it can dilate after an insult to the spinal cord to form a syringomyelia. The spinal cord is covered by three layers that provide support and suspension to the cord as well as support to the blood vessels that enter and exit.
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Moufawad and Mekhail
235
The first layer is the pia matter, which is the innermost and the thinnest of the three layers. It is in direct contact with the spinal cord. It continues with the pia matter covering the brain at the foramen magnum. It separates the CNS from the cerebrospinal fluid where it bathes. The pia matter continues with the exiting anterior and posterior roots and covers the spinal nerves resulting from fusion of anterior and posterior roots. After the spinal nerves divide into anterior and posterior primary rami, the pia merge with the endoneurium of the peripheral nerves. The middle layer is the arachnoid matter, the inner surface of which is covered by an endothelium in contact with the cerebrospinal fluid (CSF). The outer surface is formed by loose connective tissue. The outer surface of the arachnoid matter is in direct contact with the dura matter (the outermost layer). The arachnoid of the spinal cord is in continuation with the arachnoid of the brain and, therefore, the CSF bathing the brain is in continuity with the CSF bathing the spinal cord. The dura matter is the toughest of the three. It is formed by dense connective tissue. Although it is continuous with the dura of the brain, it is attached to the periosteum of the foramen magnum; this implies that the spinal epidural space is not continuous with that of the brain. The spinal epidural space contains adipose and loose connective tissues. Also, it harbors the blood vessels entering and exiting the spinal cord. The veins in the epidural space form a plexus that is continuous from the sacral to the cervical area. This plexus contains no valves, which suggests that it resembles a tube with free communication from top to bottom. (A clinical implication of this is that a metastasis from a pelvic organ is often found in the cervical epidural space and, sometimes, it is the first manifestation of the neoplasm.) The dura continues around the primary rami of the spinal nerve and merges with the epineurium at the neuroforamina. This results in a “Christmas tree” appearance of the subarachnoid space upon myelography, especially in the lumbosacral region where the exiting nerve root has a downward orientation, which occurs as a result of the sleeves of the dura around the nerve roots becoming filled with contrast dye. This layout creates three spaces delineated by the aforementioned anatomic layers: the subarachnoid space that contains the CSF, the subdural and epidural spaces. The subarachnoid space is also called the intrathecal space; however, this is a misnomer, because technically the intrathecal space is the space inside the theca or the dura matter. Anatomically, the
236 Seminars in Pain Medicine Vol. 1 No. 4 December 2003 intrathecal space encompasses the subdural and the subarachnoid spaces. The subarachnoid space is used for therapeutic purposes. The subdural space (between the dura and the arachnoid space) is a potential space that is not used clinically. However, injection of substances into this space usually leads to a wide distribution of injected solution due its small capacity; a small injection volume would travel to multiple levels and could lead to undesirable effects. For example, a 1 mL injection of an opioid into the epidural space in the lumbar region would travel two or three levels; however, in the subdural space, the same amount could easily reach the cervical level and result in respiratory depression by blocking the cervical myotomes of the phrenic nerve. The epidural space is bound by the dura centrally and the spinal canal at the periphery. (The spinal canal is lined by the periosteum of the inner surfaces of the laminae and the ligamentum flavum posteriorly; and by the posterior walls of the vertebral bodies, the posterior surfaces of the intervertebral disks, and the posterior intervertebral ligament posteriorly.) The fibers of the dura matter are aligned longitudinally; therefore, if a sharp spinal needle is used, the orientation of the needle in relation to the fibers of the dura is important, because when the bevel is oriented sideways (the cutting edges of the tip of needle are parallel with the dural fibers and can spread the fibers vs cutting them and leaving a hole, when engaging the dura) it is less damaging to the dura as compared with a bevel oriented up or down (where the cutting edges are perpendicular to the fibers and can induce more damage by cutting through the fibers). Therefore, orientation of the needle when negotiating the dura could result in a difference in the size and shape of the hole induced in the dura upon retrieval of the needle and, consequently, may affect the incidence of post– duralpuncture headache.1 The innervation of the dura is mainly on the anterior aspect, this explains why there is no pain upon dural puncture where the needle enters the dura posteriorly.
Cerebrospinal Fluid Composition The low protein content in the CSF gives it the property of low binding for substances administered, and makes these substances readily available for diffusion to the extracellular space of the CNS.
Circulation CSF is produced by the arachnoid plexus in the lateral ventricles. It travels to the third ventricle via the foramina of Monroe. From the third ventricle the CSF passes to the fourth ventricle and then exits through the foramina of Magendie and Luschka to bathe the CNS. It is then absorbed by the granulation of Paccioni, which projects from the arachnoid matter in the supratentorial area. The CSF is then drained to the venous circulation. The CSF from the lumbar area flows to the cervical area to eventually enter the skull, where it is absorbed. An important concept to consider when administering drugs into the CSF is the baricity, which is the relation of the density of the infused solution to that of the CSF. Hyperbaric solution is heavier than the CSF and, obeying the laws of the gravity, it will flow to the more dependent areas of the subarachnoid space. Hypobaric solution is less dense than CSF and therefore floats on the surface of the CSF. Isobaric solution has the same density as the CSF and does not flow preferably to different areas of the CSF. The baricity of a solution should be considered when planning therapeutic options for different patients and also for positioning of patients in relation to the region of the spinal cord where the solution is introduced. Another important consideration is the lipophilicity and hydrophilicity of the infusate. The spinal cord supporting tissue is rich in fat. Lipophilic substances tend to be stored and tend not to travel much from the point of placement. However, hydrophilic compounds tend to travel because they do not dissolve in adipose tissue. When a lipophilic substance dissolves in adipose tissue, it continues to be absorbed until it reaches an equilibrium point, where no further absorption occurs. When the concentration of the substance in the CSF starts to drop, the stored portion in the adipose tissue begins to return to the CSF or it is absorbed into the bloodstream. An important point is that when a solution is infused in the CSF, in order to reach the nerve tissues, it must cross the pia matter. Therefore, the equilibrium between concentrations of the substance between the CSF and neural tissues is a factor with regard to the lipophilicity of that substance and of its ability to traverse the pia matter. Some substances diffuse directly through membranes, whereas others have preferential transport mechanisms that move them from each side of the pia matter. The principle of affinity of the substances to the adipose tissues and water is also important when considering the epidural space as an access
Anatomy and Physiology
route to the CNS. Here the infusate is in direct contact with adipose tissues and a highly lipophilic solution will dissolve in the tissues at the point of entry until the point of equilibrium. After reaching this point of equilibrium, if the infusion continues, the solution will start to spread to the adjacent areas. However, a hydrophilic solution will travel further from the point of infusion because it is not absorbed by the fatty tissues where it is infused. This concept comes into play when planning the placement of a catheter for infusion; if the solution to be infused is lipophilic, the tip of the catheter should be placed as close to the target segment of the spinal cord as possible; otherwise, increased quantities of the solution will be needed, which may lead to a higher rate of spillage into the systemic circulation and more side effects. When using a hydrophilic solution, the tip of the catheter does not have to be as precisely placed, because the solution will be able to travel to the target area without being bound to the adipose tissues. The subarachnoid space may be used for bolus administration of substances as well as short- and long-term infusion through catheters. A typical application is administration of spinal anesthesia, where a bolus is usually administered, or with continuous long-term infusion of drugs for control of chronic pain or spasticity. A catheter inserted into the subarachnoid space could be kept indefinitely. Occlusion of the tip of the catheter by a granuloma is a rare occurrence that is not completely understood and appears related mainly to infusion of morphine.2 The epidural space is used for bolus infusion as well and for short-term infusion of medication. Long-term maintenance of a catheter in the epidural
●
Moufawad and Mekhail
237
space is not technically practical because the tip of the catheter is usually plugged by a fibrotic reaction, making it difficult to use by 3 to 4 months after insertion.3 Substances delivered to the epidural space must travel through the dura matter to the CSF and then through the pia to reach the nerve tissues. Using the epidural route as opposed to the subarachnoid route requires five- to tenfold greater levels of medication, depending on the solubility and the affinity of the dura to allow passage of substances from the epidural to the subarachnoid space. Conclusions Use of the intraspinal drug-delivery route is a safe and efficient method for controlling pain and spasticity in patients who have failed to respond to conservative treatment. The safety of the technique is directly dependent on the competence of the physician and a sound knowledge of the anatomy and physiology of the central nervous system. References 1. Mihic D: Postspinal headache and relationship of needle bevel to longitudinal dural fibers. Reg Anesth 10:76-81, 1985 2. Hassenbusch S, Burchiel K, Coffey R, et al: Management of intrathecal catheter-tip inflammatory masses: a consensus statement. Pain Med 3:313-323, 2002 3. DuPen S, Williams A: Tunneled epidural catheters: practical considerations and implantations techniques, in Waldman S, Winnie A (eds): Interventional pain management. Philadelphia, PA, Saunders, 1996, pp 457-472
Intraspinal Drug Delivery for Chronic Pain and Spasticity: Anatomic and Physiologic Considerations SAMI MOUFAWAD, MD and NAGY A. MEKHAIL, MD, PhD
ABSTRACT The intraspinal approach for controlling pain and spasticity is a safe alternative for patients who failed other less invasive modalities. It is rapidly gaining popularity as a valuable tool for this subset of patients. The safety and availability of implantable devices has helped expand the use of this route. The success of this alternative treatment is highly dependent on the physician’s skills and knowledge of the functional anatomy of the spinal cord, its coverings and its supporting structures. Key words: spinal cord, functional anatomy, physiology.
skull through the foramen magnum) to the conus medullaris. The spinal cord has two enlarged areas: in the cervical area and in the lumbosacral segment. In these areas, there is a concentration of cell bodies leading to nerves to and from the upper and lower limbs and the organs in the body cavities. The enlarged areas are the result of the volume required to accommodate these cell bodies. The thoracic segment is relatively slender compared with the other two segments, because the cell bodies supplementing the nerves to the trunk are not as numerous as those supplying the limbs. A clinical implication of these two enlargements is noted when the epidural space is approached: When advancing a catheter or a percutaneous electrode array dorsally, the tip or the catheter or electrode tend to migrate laterally to the gutter containing the dorsal nerve roots, and the operator must apply caution when steering the tip to keep it on the desired track. The conus medullaris ends at the L1-L2 interspace in an adult spine. In the fetus, the spinal cord fills the
Introduction Although the oral route is the preferred method for pain control, the intraspinal drug delivery approach is emerging as a valid alternative for patients who are unable to obtain adequate pain control using simpler methods or those who have intractable side effects. With better understanding of the mechanism of pain signal transmission, modulation, and perception, and with advances in pump technology, intraspinal infusion is becoming the state of the art in managing difficult and complicated pain problems. In addition to proper patient selection, good technique, based on sound knowledge of the anatomy and physiology of the spinal cord and its protective coverings, is the foundation of successful therapeutic intraspinal drug delivery. Such interventions should be tailored to each patient based on a good understanding of the pathology in question. When well applied and appropriately monitored, the intraspinal route of administration is very effective and associated with minimal side effects. Therefore, it is of utmost importance to start with basic discussion of the anatomy and physiology of the spinal cord.
From the Department of Pain Management, The Cleveland Clinic Foundation, Cleveland, OH. Address reprint requests to Nagy A. Mekhail, MD, PhD, Department of Pain Management, The Cleveland Clinic Foundation, 9500 Euclid Avenue, C25, Cleveland, OH 44195. E-mail: [email protected] © 2004 Elsevier Inc. All rights reserved. 1537-5897/04/0104-0007/$30.00/0 doi:10.1016/j.spmd.2004.02.005
Anatomy of the Spinal Cord The spinal cord is the part of the central nervous system extending from the brain stem (exiting the
234
Anatomy and Physiology
vertebral canal. Upon development into adulthood, the bony and ligamentous structures of the spine develop faster than the nervous system, which results in a spinal canal that is longer than the spinal cord. This also explains the downward orientation of the spinal roots, leaving the spinal cord and heading to the corresponding neuroforamina. This downward orientation of the spinal roots is more obvious at the lumbar and sacral regions compared with the cervical and thoracic regions. The conus medullaris is anchored by the filum terminale that is formed by connective tissue and does not contain neural elements. The filum is covered by the pia matter and extends with the cauda equina inside the spinal canal in the subarachnoid space and attaches to the lower end of the spinal canal at the level of the coccyx. The cauda equina (“horse tail”) is the collection of paired nerve roots traveling in the lower end of the spinal canal. The individual nerves are attached to the spinal cord cephalad, and to the corresponding neuroforamen caudad. Functionally, the spinal cord plays a role in connecting the brain to the nerve roots and the peripheral nervous system. It also houses reflex circuits at multiple levels, which play a role in controlling different body functions to include a critical role in the regulation of pain perception, signal transmission, and muscle tone. The spinal cord segmental circuitry modifies the signals transmitted in both directions. The spinal cord is formed by the nerve fibers, cell bodies, and supporting structures. Clusters of cell bodies form nuclei at multiple levels of the spinal cord. The fibers serve as a connection between these nuclei and also transmit signals from the periphery to the central nervous system (CNS) and vice versa. The gross anatomy of the spinal cord is composed mainly of gray and white matter where the gray is mainly central in the form of the letter “H.” This is mainly where the nuclei and cell bodies are located. The gray matter is surrounded by white matter (it is white due to the myelin sheaths covering the nerve fibers running throughout the area). In the center of the spinal cord is a small diameter canal called the ependymal canal. In the embryo the spinal cord develops as a plate that folds and closes to form a tube, the ependymal canal is the rudimentary lumen of that tube. This tube is blind distally and communicates with the fourth ventricle proximally. It does not have any clinical indication except that it can dilate after an insult to the spinal cord to form a syringomyelia. The spinal cord is covered by three layers that provide support and suspension to the cord as well as support to the blood vessels that enter and exit.
●
Moufawad and Mekhail
235
The first layer is the pia matter, which is the innermost and the thinnest of the three layers. It is in direct contact with the spinal cord. It continues with the pia matter covering the brain at the foramen magnum. It separates the CNS from the cerebrospinal fluid where it bathes. The pia matter continues with the exiting anterior and posterior roots and covers the spinal nerves resulting from fusion of anterior and posterior roots. After the spinal nerves divide into anterior and posterior primary rami, the pia merge with the endoneurium of the peripheral nerves. The middle layer is the arachnoid matter, the inner surface of which is covered by an endothelium in contact with the cerebrospinal fluid (CSF). The outer surface is formed by loose connective tissue. The outer surface of the arachnoid matter is in direct contact with the dura matter (the outermost layer). The arachnoid of the spinal cord is in continuation with the arachnoid of the brain and, therefore, the CSF bathing the brain is in continuity with the CSF bathing the spinal cord. The dura matter is the toughest of the three. It is formed by dense connective tissue. Although it is continuous with the dura of the brain, it is attached to the periosteum of the foramen magnum; this implies that the spinal epidural space is not continuous with that of the brain. The spinal epidural space contains adipose and loose connective tissues. Also, it harbors the blood vessels entering and exiting the spinal cord. The veins in the epidural space form a plexus that is continuous from the sacral to the cervical area. This plexus contains no valves, which suggests that it resembles a tube with free communication from top to bottom. (A clinical implication of this is that a metastasis from a pelvic organ is often found in the cervical epidural space and, sometimes, it is the first manifestation of the neoplasm.) The dura continues around the primary rami of the spinal nerve and merges with the epineurium at the neuroforamina. This results in a “Christmas tree” appearance of the subarachnoid space upon myelography, especially in the lumbosacral region where the exiting nerve root has a downward orientation, which occurs as a result of the sleeves of the dura around the nerve roots becoming filled with contrast dye. This layout creates three spaces delineated by the aforementioned anatomic layers: the subarachnoid space that contains the CSF, the subdural and epidural spaces. The subarachnoid space is also called the intrathecal space; however, this is a misnomer, because technically the intrathecal space is the space inside the theca or the dura matter. Anatomically, the
236 Seminars in Pain Medicine Vol. 1 No. 4 December 2003 intrathecal space encompasses the subdural and the subarachnoid spaces. The subarachnoid space is used for therapeutic purposes. The subdural space (between the dura and the arachnoid space) is a potential space that is not used clinically. However, injection of substances into this space usually leads to a wide distribution of injected solution due its small capacity; a small injection volume would travel to multiple levels and could lead to undesirable effects. For example, a 1 mL injection of an opioid into the epidural space in the lumbar region would travel two or three levels; however, in the subdural space, the same amount could easily reach the cervical level and result in respiratory depression by blocking the cervical myotomes of the phrenic nerve. The epidural space is bound by the dura centrally and the spinal canal at the periphery. (The spinal canal is lined by the periosteum of the inner surfaces of the laminae and the ligamentum flavum posteriorly; and by the posterior walls of the vertebral bodies, the posterior surfaces of the intervertebral disks, and the posterior intervertebral ligament posteriorly.) The fibers of the dura matter are aligned longitudinally; therefore, if a sharp spinal needle is used, the orientation of the needle in relation to the fibers of the dura is important, because when the bevel is oriented sideways (the cutting edges of the tip of needle are parallel with the dural fibers and can spread the fibers vs cutting them and leaving a hole, when engaging the dura) it is less damaging to the dura as compared with a bevel oriented up or down (where the cutting edges are perpendicular to the fibers and can induce more damage by cutting through the fibers). Therefore, orientation of the needle when negotiating the dura could result in a difference in the size and shape of the hole induced in the dura upon retrieval of the needle and, consequently, may affect the incidence of post– duralpuncture headache.1 The innervation of the dura is mainly on the anterior aspect, this explains why there is no pain upon dural puncture where the needle enters the dura posteriorly.
Cerebrospinal Fluid Composition The low protein content in the CSF gives it the property of low binding for substances administered, and makes these substances readily available for diffusion to the extracellular space of the CNS.
Circulation CSF is produced by the arachnoid plexus in the lateral ventricles. It travels to the third ventricle via the foramina of Monroe. From the third ventricle the CSF passes to the fourth ventricle and then exits through the foramina of Magendie and Luschka to bathe the CNS. It is then absorbed by the granulation of Paccioni, which projects from the arachnoid matter in the supratentorial area. The CSF is then drained to the venous circulation. The CSF from the lumbar area flows to the cervical area to eventually enter the skull, where it is absorbed. An important concept to consider when administering drugs into the CSF is the baricity, which is the relation of the density of the infused solution to that of the CSF. Hyperbaric solution is heavier than the CSF and, obeying the laws of the gravity, it will flow to the more dependent areas of the subarachnoid space. Hypobaric solution is less dense than CSF and therefore floats on the surface of the CSF. Isobaric solution has the same density as the CSF and does not flow preferably to different areas of the CSF. The baricity of a solution should be considered when planning therapeutic options for different patients and also for positioning of patients in relation to the region of the spinal cord where the solution is introduced. Another important consideration is the lipophilicity and hydrophilicity of the infusate. The spinal cord supporting tissue is rich in fat. Lipophilic substances tend to be stored and tend not to travel much from the point of placement. However, hydrophilic compounds tend to travel because they do not dissolve in adipose tissue. When a lipophilic substance dissolves in adipose tissue, it continues to be absorbed until it reaches an equilibrium point, where no further absorption occurs. When the concentration of the substance in the CSF starts to drop, the stored portion in the adipose tissue begins to return to the CSF or it is absorbed into the bloodstream. An important point is that when a solution is infused in the CSF, in order to reach the nerve tissues, it must cross the pia matter. Therefore, the equilibrium between concentrations of the substance between the CSF and neural tissues is a factor with regard to the lipophilicity of that substance and of its ability to traverse the pia matter. Some substances diffuse directly through membranes, whereas others have preferential transport mechanisms that move them from each side of the pia matter. The principle of affinity of the substances to the adipose tissues and water is also important when considering the epidural space as an access
Anatomy and Physiology
route to the CNS. Here the infusate is in direct contact with adipose tissues and a highly lipophilic solution will dissolve in the tissues at the point of entry until the point of equilibrium. After reaching this point of equilibrium, if the infusion continues, the solution will start to spread to the adjacent areas. However, a hydrophilic solution will travel further from the point of infusion because it is not absorbed by the fatty tissues where it is infused. This concept comes into play when planning the placement of a catheter for infusion; if the solution to be infused is lipophilic, the tip of the catheter should be placed as close to the target segment of the spinal cord as possible; otherwise, increased quantities of the solution will be needed, which may lead to a higher rate of spillage into the systemic circulation and more side effects. When using a hydrophilic solution, the tip of the catheter does not have to be as precisely placed, because the solution will be able to travel to the target area without being bound to the adipose tissues. The subarachnoid space may be used for bolus administration of substances as well as short- and long-term infusion through catheters. A typical application is administration of spinal anesthesia, where a bolus is usually administered, or with continuous long-term infusion of drugs for control of chronic pain or spasticity. A catheter inserted into the subarachnoid space could be kept indefinitely. Occlusion of the tip of the catheter by a granuloma is a rare occurrence that is not completely understood and appears related mainly to infusion of morphine.2 The epidural space is used for bolus infusion as well and for short-term infusion of medication. Long-term maintenance of a catheter in the epidural
●
Moufawad and Mekhail
237
space is not technically practical because the tip of the catheter is usually plugged by a fibrotic reaction, making it difficult to use by 3 to 4 months after insertion.3 Substances delivered to the epidural space must travel through the dura matter to the CSF and then through the pia to reach the nerve tissues. Using the epidural route as opposed to the subarachnoid route requires five- to tenfold greater levels of medication, depending on the solubility and the affinity of the dura to allow passage of substances from the epidural to the subarachnoid space. Conclusions Use of the intraspinal drug-delivery route is a safe and efficient method for controlling pain and spasticity in patients who have failed to respond to conservative treatment. The safety of the technique is directly dependent on the competence of the physician and a sound knowledge of the anatomy and physiology of the central nervous system. References 1. Mihic D: Postspinal headache and relationship of needle bevel to longitudinal dural fibers. Reg Anesth 10:76-81, 1985 2. Hassenbusch S, Burchiel K, Coffey R, et al: Management of intrathecal catheter-tip inflammatory masses: a consensus statement. Pain Med 3:313-323, 2002 3. DuPen S, Williams A: Tunneled epidural catheters: practical considerations and implantations techniques, in Waldman S, Winnie A (eds): Interventional pain management. Philadelphia, PA, Saunders, 1996, pp 457-472