Trials and their applicability

Intrathecal infusion trials

One of the biggest advances in the treatment of pain of malignant origin is the use of intraspinal narcotics. Due to this change, less neurodestructive surgery is performed as a palliative procedure on this patient population. With the success of intrathecal therapy for malignant pain, it was a smooth transition to utilizing this therapy for chronic nonmalignant pain.

Over the past decade, intrathecal infusion pumps have become technologically sophisticated, and both Food and Drug Administration approved drugs and other medications are being commonly used to treat a variety of chronic painful conditions. Basically, there are six types of implantable drug delivery systems ranging from a simple percutaneous catheter system to a totally implanted programmable pump with the ability to administer boluses of medications. Each system has advantages and disadvantages. It is the responsibility of the practitioner to determine the optimal and simplest system that will adequately treat the pain patient. With each system, cost increases as the complexity of the system increases and the cost is likely to be scrutinized by insurers in the future. Once the system is implanted, monthly expenditures continue as the need for medication refills and refill supplies (i.e., needles, tubing, syringes) continue. The practitioner and patient are linked together and will likely remain in a long-term relationship.

The availability of implanted pumps for intrathecal infusion has provided an important alternative therapy for patients unable to tolerate side effects of systemically administered medications. A concentration gradient forms when a substance is infused into the subarachnoid space of the spinal cord, with the concentration being highest at the tip of the catheter and decreasing rapidly as the distance from the catheter tip increases. Drug concentrations should be lower in the Cerebrospinal Fluid (CSF) surrounding the brain and extremely low in peripheral tissues. This is the reason for decreased side effects and sedation with intrathecally administered medications.

Prior to proceeding with the trial, the patient needs to have a thorough evaluation and correct diagnosis. The patient's current therapeutic regimen needs to be analyzed and deemed appropriate. The extent of the pain problem and disease and the likelihood of progression need to be taken into consideration. Any oncologic therapy in the case of malignant pain needs to be optimized prior to proceeding with the trial. A preimplantation trial of spinal opioids is necessary to determine whether an implantable system will adequately relieve the patient's pain. Not all pain is relieved by spinal opioids. It is required that the opioids relieve the patient's pain on two separate occasions during the trial period and that the degree of relief be greater than 50%. In addition, the duration of relief should last at least twice the duration of the half-life of the therapeutic agent. In the case of morphine, the duration of relief should last 8–12 hours.

Trials of opioids may fail for a number of reasons. The medication may have been deposited in the wrong location, or there may be psychological barriers to the testing process, that is, major depression or a severe anxiety disorder. In addition, the incorrect dose of medication may have been chosen or the patient may have developed an extreme tolerance to opioids prior to the trial period. The pain may not be responsive to spinal narcotics, that is, central pain syndromes and, if any questions remain, a trial of a placebo injection, may clarify the situation. The response to acute drug administration is predictive of long-term outcome and success in chronic intraspinal therapy.

Pump selection

Two major classes of implanted pumps have been designed for intrathecal infusion therapy. Constant flow pumps rely on a fairly constant pressure exerted by a gas on a diaphragm, forcing a constant stream of medication from the reservoir through a small orifice. Programmable pumps are extremely accurate and reliable. Any infusion rate within the volume capabilities of the pump may be programmed. In addition, complex continuous infusions with a daily bolus and/or varying infusion rates throughout the day may be programmed.

Indications

Patient selection for continuous intrathecal morphine therapy is not as well defined as for SCS. Most candidates are patients with intractable pain conditions that have failed to respond to conservative therapies and have failed chronic opioid therapy due to either excessive side effects and/or inadequate analgesia. Candidates should have a life expectancy of at least 3 months before an implantable pump is considered. There are no other simple rules for choosing appropriate candidates. Nearly all patients will receive substantial relief from a test dose or infusion trial. Many will develop significant tolerance to intrathecal opioids after 1–2 years of infusion therapy such that pain relief is only mildly improved from preimplant levels.

Choosing patients for intrathecal baclofen therapy is much more straightforward than selection for intrathecal opiate therapy. Patients with spasticity of central origin who have failed oral baclofen therapy and at least one other appropriate antispasmodic agent are suitable candidates. The types of patients vary from those who will be able to ambulate more easily if the therapy is successful to those who will remain bedridden but will be easier to care for.

Patients are generally referred by a neurologist or neurosurgeon for an intrathecal baclofen trial. Single shot intrathecal test doses are given in a monitored setting where the patient's response to the injection can be observed on an hourly basis for 8 hours. Response may be rated with the Ashworth scale and by observing functional ability. Some patients rely on the spasticity of certain muscle groups for ambulation and arm movement. Function in these cases may worsen as spasticity improves. Test dosing begins at 50 mg. Doses of 75 and 100 mg may be given on subsequent days if the initial dose produces no results. If the patient does not respond to a 100 mg test dose, implantation is not a viable option.

Patient selection

Patient selection is the most important part of the preimplant process. Experience indicates that a structured approach to the preimplant phase facilitates the best possible experience for patient and practitioner. The clinician should establish a checklist algorithm to ensure that each patient has experienced a complete preimplantation evaluation. Careful selection of patients improves outcome results and builds trust in the patient–clinician relationship.

Important components of the preimplantation checklist include determining if the patient meets appropriate criteria. Appropriate criteria include

• Ineffective oral analgesia with multiple oral or transcutaneous trials including dose titrations

• Intolerable side effects despite adequate rotation of opioids

• Intractable spasticity unrelieved by oral antispasmodics with improved Ashworth scores at baclofen test dose

• Access to care

• Functional analgesia during temporary trial infusion

• Psychological stability and realistic postimplant goals

Patient acceptance

An appropriate preimplant checklist includes

• Does the patient meet appropriate patient selection criteria?

• Has the patient been cleared by a knowledgeable psychologist?

• Did the patient achieve a 50% or greater reduction in pain during the trial infusion?

• Did the patient have appropriate occupational and physical therapy evaluations during the trial that showed acceptable functional gains?

• Did the patient have preoperative teaching?

• Was the infection risk assessment completed and discussed with the patient and family?

The patient must be physically able to have the pump and catheter implanted. In some cases, the patient may have had very extensive spinal or abdominal surgery which can increase the level of surgical complexity. The patient must be evaluated for access to the intrathecal or epidural space, and access to a site suitable for pump implantation. Patient positioning may be an issue secondary to anatomical factors. The patient will need to be placed in the lateral decubitus position with the pump side up during the implant procedure.

The risk of intraspinal catheters and pump implantation should not be ignored. The risks are manageable and, in experienced hands, are limited. General risks include infection, postdural puncture headache, catheter-related epidural infections, granuloma formation, dose escalation and tolerance, and serious withdrawal symptoms due to pump or catheter failure (clonidine and baclofen).

Needle placement for intrathecal pump placement introduction

An intrathecal pump system is implanted via a sterile surgical procedure performed under local, regional, or general anesthesia. The implant procedure typically lasts from 2 to 4 hours. Prior to the procedure, a complete preoperative physical examination should have been performed and the patient should be educated as to the procedure and the associated risks.

Preoperative preparation

Before the implantation procedure, the physician and patient need to spend some time deciding on the side and location of the pump. It is usually placed in the left or right lower quadrant of the abdomen. It is placed so that it does not contact the iliac crest, pubic symphysis, ilioinguinal ligament, or the costal margin.

Preoperative antibiotics are given in the holding area. Usually, a cephalosporin is adequate and should be completely infused prior to the patient's transportation to the operating suite.

Anesthesia

Implantation of the catheter and subsequent pump placement may take place with the patient under general or local anesthesia with monitoring. Local anesthesia, in conjunction with sedation, is often preferred in the outpatient setting. When general anesthesia is chosen, the use of muscle relaxants is usually avoided until after the catheter is passed into the intrathecal space.

Procedure