Intrathecal drug delivery systems are typically used for three main purposes, which are the treatment of chronic non-malignant pain, muscle spasticity, and cancer-related pain. This activity reviews the indications, contraindications, and technique involved in the implantation of an intrathecal drug delivery system and highlights the role of the interprofessional team in the care of patients undergoing this procedure.
Identify the indications for implantation of intrathecal drug delivery system.
Outline the steps involved in implantation of an intrathecal drug delivery system.
Describe the mechanism of action for each of the three medications approved for intrathecal use.
Explain a structured, interprofessional team approach to provide effective care to and appropriate surveillance of patients undergoing implantation of an intrathecal drug delivery system.
Chronic pain is a complex condition, characterized by changes in the nervous system and clinical manifestations that are influenced by psychosocial and potentially iatrogenic factors. When the nociceptive system is repeatedly activated, peripheral and central neural pathways that normally convert noxious environmental stimuli into perceived pain in the brain can become abnormally sensitized. These abnormal pathways can present clinically as severe, persistent, and functionally disabling pain, which is often challenging to manage despite individualized care with oral medications and psychosocial treatments. Attaining good outcomes for patients with severe chronic pain has recently become even more difficult because of the critical safety concerns and public health issues associated with prescription opioids. When patients cannot reach their analgesic and functional goals with more conventional therapies, their clinicians should contemplate advanced pain management options. One interventional modality involves delivering analgesics directly into the intrathecal cerebrospinal fluid (CSF) via pump and catheter. The first pump providing low-dose morphine in a patient with cancer-related pain was implanted in 1981. Since that time, a number of systematic reviews have found intrathecal drug delivery systems (IDDS) to be effective and safe for cancer-related and chronic noncancer pain.
Anatomy and Physiology
An intrathecal drug delivery system consists of two parts, a pump, and an intrathecal catheter. The pump serves as the drug reservoir, and it is implanted under the subcutaneous tissue in the abdominal area. The second is the catheter which attaches to the pump and delivers medications directly into the intrathecal space. Generally, catheter tip placement is at the level of the spinal cord that innervates the body region comprising the primary pain generator. Once in the CSF, intrathecally delivered medications permeate across the pia-arachnoid and white matter of the spinal cord to access the target dorsal horn receptors and ion channels engaged in nociceptive processing and transmission.
To date, three medications have been specifically authorized by the US Food and Drug Administration (FDA) for intrathecal delivery. Morphine is a mu-opioid receptor agonist that utilizes its spinal effects by binding to receptors in the substantia gelatinosa located in the dorsal column. Pre and post-synaptic receptor activation with morphine yields to the dampening of ascending pain-related neural activity. The second FDA-approved approved intrathecal analgesic is ziconotide, a potent drug derived from the neuro-toxic venom of cone snails. Ziconotide exerts its analgesic effect by reversibly antagonizing the pre-synaptic N-type voltage-gated calcium channels expressed by nociceptive neurons in the dorsal horn. The third approved medication is baclofen, which is used to treat muscle spasticity from a variety of conditions such as multiple sclerosis and cerebral palsy.
Implantable drug delivery systems are usually reserved for patients whose condition is considered chronic and in whom conventional approaches are insufficient or not tolerated. Patients typically have poor pain control or intolerable side effects on systemic opiates and non-opioid adjuvant therapy. The implantation of a pump should be part of a treatment sequence based on specific selection criteria. Although the patient does not need to meet every criterion for implantation, the following should merit consideration:
Patient has an expected 3 months survival (at least)
Failed conservative treatments
Has a trial of neuraxial medication(s) that provides acceptable pain relief (greater than 50%)
Tolerable side effects
Has favorable spinal anatomy that will allow for spinal catheter placement
Is both medically and mentally stable without untreated infectious and psychiatric conditions
Intrathecal therapy has been used successfully for chronic cancer pain as well as chronic non-malignant pain.
Cancer indications include primary tumors and metastatic tumors generating pain from tissue invasion, chemotherapy-induced neuropathy, and radiation-induced nerve injury. Noncancer indications include failed back surgery syndrome, spinal canal and foraminal stenosis, compression fractures, peripheral neuropathy, truncal pain, axial pain, complex regional pain syndrome, and connective tissue disorders. The decision to place an intrathecal pump should be a well thought out process. A discussion should take place between the physician and patient regarding the details of pump placement, including its risks and benefits. An algorithmic approach is necessary for pump therapy, where the patient should meet acceptable selection criteria and indications before pump placement. As with any medical intervention, the identification of appropriate candidates is critical to maximizing the chances of clinical benefit.
There are several contraindications for IDDS therapy, and these can subdivide into absolute and relative exclusion criteria. Absolute contraindications include systemic infection, known allergies to materials in the implant, active intravenous drug abuse, psychosis or dementia, and infection at the implantation site. Relative contraindications include an atrophied patient (underweight BMI), ongoing anticoagulation that cannot be discontinued, active bleeding, high opioid tolerance, lack of social or family support, and lack of access to medical care. Intrathecal pump placement is an elective procedure; thus one must assess all potential absolute and relative contraindications before proceeding.
The necessary equipment needed for intrathecal drug delivery implantation includes
An implantable intrathecal infusion pump
Appropriate surgical instruments for implantation
Local anesthetics for infiltration
Drug to be used for intrathecal infusion
External programmer for pump
See technique for details
Intrathecal delivery system implantation is typically performed primarily by neurosurgeons, interventional pain management physicians, and orthopedic spine specialists. Intraoperative personnel may also include a fluoroscopy technician and nurse. Most patients will need to undergo general anesthesia to have their device implanted and therefore an anesthesiology team should be present.
Before any spinal procedure, a thorough physical exam and neurological exam should be performed.
Imaging is essential in assessing spinal anatomy to determine the location of needle placement and catheter placement. Magnetic resonance imaging (MRI) of the patient's spine should be obtained and reviewed before the procedure. This will allow the surgeon performing the implant to determine if there is any anatomical obstruction to needle or catheter placement and if the patient's spinal anatomy will allow for placement of a spinal catheter. The optimal needle and catheter entry point is typically below the level of the conus medullaris between the L2 to S1 lumbar interspaces. For this reason, an MRI of the lumbar spine is necessary and depending on where the surgeon desires the tip of the catheter placement, a thoracic and/or cervical MRI should be acquired as well.
Laboratory studies that require assessment include a complete blood count with platelets, prothrombin time, partial thromboplastin time, platelet function studies, and bleeding time. If the patient is taking any anticoagulants, there should be a clearance from the medical team to stop these medications before the surgery. Most patients are placed under general anesthesia and positioned in the lateral decubitus position for optimal access to the abdominal and spinal areas. If the patient elects to forgo general anesthesia, then the standard recommendations for conscious sedation by the American Society of Anesthesiologists should be followed. Advantages of conscious sedation for the procedure include a potentially lower risk of spinal cord or nerve root damage as the patient can communicate during the surgery which allows for the real-time assessment of neurologic status. Many surgeons prefer general anesthesia for implantation as this can be a painful and anxiety-provoking procedure. Further, an excessive patient movement could increase the difficulty of the surgery and lead to further complications.
Antibiotic prophylaxis is achieved with the administration of weight-based intravenous cefazolin 1 hour prior to incision. Typically vancomycin is administered if the patient is cefazolin allergic.
A detailed discussion of the risks and benefits of the procedure should undergo a review with the patient before pump placement.
Before implantation, time should be spent with the patient to decide on the side and location of the pump. Currently, the only on-label location for implantation is the right or left lower quadrant of the abdomen. The anatomical boundaries tend to be the iliac crest and costal margin, as these areas should not make contact with the pump post-implantation. The following steps should be carried out:
1) After the type of anesthesia is decided, position the patient in the lateral decubitus position on the operating room table with the side of pump implantation upward. The back and abdomen should be sterile prepped and draped. The C-arm is necessary to confirm access to the intrathecal space and for positioning of the catheter tip.
2) Position the C-arm to allow for the appropriate anterior-posterior view, allowing easy lumbar puncture, visualization of catheter threading and pinpointing tip position.
3) Make a small incision in the skin down to the dorso-lumbar fascia in the spine to expose the supraspinous ligament. Through the exposed tissue, place a Tuohy needle into the intrathecal space using a paramedian approach. Whenever possible, the intrathecal space should be entered below the level where the spinal cord ends (L1 or L2) to avoid possible spinal cord injury. A slight cephalad needle angle optimizes cerebrospinal fluid (CSF) flow and decreases the risk of catheter kink or fracture. Upon documentation of adequate CSF flow, thread the catheter through the Tuohy needle confirming catheter and catheter tip position with intermittent fluoroscopy. Place two fascial sutures on either side of the Tuohy needle. During this suturing step keep the Tuohy needle in place to prevent accidental catheter damage. Once final catheter tip positioning is confirmed, remove the introducer Tuohy needle, withdrawing the needle and guidewire together leaving just the catheter in place. Again recheck CSF back-flow. Insert the catheter into an anchor and secure it with fascial sutures. After securing the catheter to the dorso-lumbar fascia, clamp the distal intrathecal catheter to prevent CSF loss.
4) Turn attention to the lower quadrant of the abdomen. Make an approximately 8cm lengthwise incision down to the underlying subcutaneous fat layer. Create a subcutaneous pocket large enough to contain the pump being used. Generally, if all four fingers can fit into the pocket, it is large enough and allows closure without tension. The depth of the pocket below the skin is critical for programmable pumps. A depth of greater than 2.5 cm may not allow reliable telemetry and will make pump refilling more difficult.
5) It is important to maintain hemostasis in both incision sites to avoid postoperative hematoma formation. Irrigate pockets with antibiotic solution.
6) Next, assemble the malleable tunneling device and prepare a subcutaneous tunnel from midline back incision to the pump pocket. Once there is a successful placement of the tunneling device, push the catheter through the tunnel to the abdominal pocket.
7) Cut any excess catheter but be sure to ensure adequate length for a stress relief loop in the midline incision and pump pocket. If the catheter length is too long, this may increase susceptibility to catheter kinking.
8) Attach the catheter to the pump nipple and verify that it is secure.
9) Place programmable pump into the subcutaneous pocket. Stitches may be placed through the anchoring loops of the pump to prevent rotation. If this technique is used, place the stitches into the pocket first, then through the pump suture loops.
10) Carefully close the pocket and spinal incisions with suture. Proximate the skin edges with steri-strips. If tension is a problem, use surgical staples to reinforce the incision site closure.
Complications associated with the intrathecal delivery system can subdivide into surgery-related complications and device-related complications. Surgery-related complications generally occur in the perioperative period. Possibly the most worrisome and avertible surgery-related complication is a pump pocket hematoma. Focusing on hemostasis during pocket formation can potentially prevent this complication. Placing an abdominal binder around the abdomen for modest compression in the early postoperative period can prevent blood or fluid buildup. Another surgical related complication is the likelihood for an epidural or intrathecal bleed with associated neurologic sequelae. To decrease the risk of this complication, preoperatively, care should be taken to reverse any anticoagulation and stop any nonsteroidal anti-inflammatory drug use.
Signs of a developing hematoma include a precipitous increase in back pain, progressive numbness, and weakness in the lower extremities, and loss of bowel and bladder control. This clinical presentation justifies immediate MRI or CT myelography scanning and emergent surgical decompression if there is neurologic deterioration. An additional surgery-related complication is wound infection. Prophylactic antibiotics and intraoperative antibiotic irrigation can likely protect against this. Furthermore, consideration on the part of the ancillary surgical staff to manage all aspects with care and avoid contamination will also help limit infection. Unless the infection is superficial, wound infections require explantation of the device. Infection can track along the intrathecal catheter and can cause either meningitis or an epidural abscess.
Neurologic injury is a risk whenever there is penetration of the CSF space. Needle placement, even when guided fluoroscopically, is truly "blind" with respect to intraspinal neural structures. Injury to the nerve roots can occur. However, the placement of the catheter under conscious sedation can decrease this risk. Because they are awake, the patient under conscious sedation can report a shock-like or burning sensation in the distribution of the involved nerve root. In response, the needle should be promptly withdrawn and placed at a different level. Aside from needle placement, catheter placement also puts the spinal cord at risk. Catheters are designed with some stiffness so they can be steered through the intrathecal space. The catheter must not be forced through the spinal canal because the tip may end up in an intramedullary position.
Penetration of the spinal cord often results in dysesthesias or burning, stinging pain below the lesion and neurological signs are usually observable immediately. Intramedullary infusion of the drug may result in developing signs of a spinal cord lesion and should be immediately evaluated with MRI or CT myelography and evaluated by a neurosurgeon. CSF leaks are a probable consequence of placing catheters in the intrathecal space. The opening developed in the dura mater by introducing a needle larger than the entering catheter predisposes to leakage. This leakage can precipitate into a post-dural puncture headache. This headache should initially be managed conservatively with fluids, maintaining a supine position, increased caffeine intake, and utilizing non-narcotic analgesics such as acetaminophen. If the headache is refractory to conservative management, a blood patch consisting of 10 to 20ml of autologous venous blood injected one level above the catheter entry point under fluoroscopic guidance (to avoid catheter shearing), should treat the headache effectively.
Device-related complications typically involve either the catheter system or the pump. Catheter-related complications are more frequent than pump complications . Catheter tip obstruction can be an issue and may require revision of the catheter. This problem is commonly suspected when the expected and measured residual volumes differ by more than 20%, and/or there is a fluctuation of analgesic effectiveness reported by the patient. A comprehensive evaluation of the catheter is necessary if there is suspicion for kinking, obstruction, or separation. This is done via basic imaging and/or a catheter study by injecting contrast dye via the pump side port. Injecting contrast can display the point of kinkage, obstruction or leakage. Aspiration of the catheter should occur before injecting contrast dye to avoid delivering a large dose of medication into the intrathecal space which can lead to overdosage. Intrathecal granulomas can also cause catheter tip obstruction. In addition to obstruction, they may also create increasing pain and a developing neurologic deficit. The risk of granuloma progression seems to correlate directly with the daily opioid dose, the rate of drug titration, and the duration of intrathecal therapy. If a granuloma is presumed, the diagnosis should be confirmed using an MRI preferably with contrast. If a granuloma is present, the precipitating medication should be decreased or eliminated with discretion to avoid withdrawal symptoms, and a neurosurgical consult may be necessary.
In summary, intrathecal drug delivery provides the advantage of using comparably low daily dosages to achieve the desired analgesic effect. This procedure translates to lower drug elimination for the patient and diminished systemic side effects relative to oral or intravenous administration of the same agent. Moreover, the programmed pump regulates the infusion rate throughout the day to eliminate the peaks and troughs in plasma drug levels as seen with oral dosing.
Enhancing Healthcare Team Outcomes
It is vital to recognize that chronic pain conditions for which intrathecal drug delivery is appropriate are optimally managed by an integrated health care team. Intrathecal therapy and management can substantially lower health care costs compared with conventional pain management, especially when there is a cessation of systemic opioids. To attain beneficial patient-centric care, the supervising clinician should oversee pump refills and medication adjustments after patient evaluation. The new application of the Polyanalgesic Consensus Conference (PACC) guidelines, which has its basis level 1 evidence, randomized controlled trials and prospective observational studies, contain algorithms intended to guide intrathecal medication choices for localized or diffuse nociceptive or neuropathic pain for patients with cancer, terminal illness, and noncancer pain.
The guidelines emphasize the necessity for provider education across health care settings and specialties to address the expanding evidence related to intrathecal drug delivery for chronic pain. Protocols for the patient and IDDS management should be assembled around a collaborative team-based care model that provides ongoing education for patients and caregivers, along with the proper use of psychosocial support services. A patient-centered approach can lend to encouraging outcomes among patients with refractory chronic pain. All nurses who look after patients with an intrathecal pump should have an orientation and a seminar to ensure that they are fully aware of the potential complications.
(Click Image to Enlarge)
Left Image Intrathecal catheter lateral view: fluoroscopic picture of catheter in intrathecal space
Right Image IT catheter paramedian approach: characteristic paramedian Tuohy needle approach to obtain intrathecal access
Images Contributed by Dr. Devang Padalia
Prager J,Deer T,Levy R,Bruel B,Buchser E,Caraway D,Cousins M,Jacobs M,McGlothlen G,Rauck R,Staats P,Stearns L, Best practices for intrathecal drug delivery for pain. Neuromodulation : journal of the International Neuromodulation Society. 2014 Jun; [PubMed PMID: 24446870]
Deer T,Winkelm�ller W,Erdine S,Bedder M,Burchiel K, Intrathecal therapy for cancer and nonmalignant pain: patient selection and patient management. Neuromodulation : journal of the International Neuromodulation Society. 1999 Apr; [PubMed PMID: 22151109]
Deer TR,Smith HS,Cousins M,Doleys DM,Levy RM,Rathmell JP,Staats PS,Wallace M,Webster LR, Consensus guidelines for the selection and implantation of patients with noncancer pain for intrathecal drug delivery. Pain physician. 2010 May-Jun; [PubMed PMID: 20495597]
Hatheway JA,Caraway D,David G,Gunnarsson C,Hinnenthal J,Ernst AR,Saulino M, Systemic opioid elimination after implantation of an intrathecal drug delivery system significantly reduced health-care expenditures. Neuromodulation : journal of the International Neuromodulation Society. 2015 Apr; [PubMed PMID: 25688677]