IMPLANTATION TECHNIQUES AND POSTOPERATIVE MANAGEMENT FOR INTRATHECAL DRUG DELIVERY

Once intrathecal drug delivery has been selected as an appropriate therapy for a patient with chronic pain, the patient must go through a screening test to help predict the level of response to the therapy. The intrathecal drug delivery screening test has two stages:
● Delivery of a pain-relieving drug such as morphine to the patient’s intraspinal space
● Longer-term patient evaluation

The screening test
The delivery of a pain-relieving drug to the patient’s epidural or intrathecal space is the first stage of the intrathecal drug delivery screening test, and often takes place on an outpatient basis. Physicians may elect to gradually withdraw or decrease a patient’s systemic opioids before the screening test to reduce the overall steroid burden and to allow a more accurate reading. However, patients may continue to take certain medications, including oral morphine during the screening test, if the physician deems it necessary. The physician will determine the protocol for the screening test.

Possible protocols
The exact screening protocol is derived at the discretion of the physician. However, screening trial techniques can generally be categorized as follows:
● Single bolus injection
● Multiple injections
● Continuous infusion

Table 1: Screening trial techniques
Method	Description
Single bolus injection	● The patient is injected with a single bolus of a pain-relieving drug into the intrathecal space via a lumbar puncture ● The dose is usually 0.5 to 1.0 mg or the intrathecal equivalent of the patient’s daily (systemic) narcotic intake
Multiple injections	● The patient is administered a series of injections, either intrathecally or epidurally ● For epidural administration, injections are administered via an epidural catheter inserted under fluoroscopy to ensure proper placement ● Patients may receive a placebo to accurately assess symptom relief
Continuous infusion	● A catheter is placed either intrathecally or epidurally and connected to an external infusion pump ● The effectiveness and tolerability of the drug is tested over a period of days to weeks. The initial dose is 0.2 mg/hour or the epidural equivalent of the patient’s daily (systemic) narcotic intake. The dose is increased every 12 to 14 hours until pain relief is reported ● The advantage of this method is that continuous infusion can more closely mimic an implantable system, and response can be assessed during the patient’s normal daily activities

Physicians may choose one of several variations of the above protocol. For example, physicians may choose to administer the bolus injection into the patient’s epidural space rather than the intrathecal space. The physician may also choose to repeat the bolus injection method by repeating the injection every 8–12 hours, increasing the daily dose, until adequate pain relief is achieved. Variations of the protocol impact on the duration of the screening test, which can be accomplished within 23 hours using a bolus injection or within a few days or weeks using continuous infusion.
During the screening test the physician will observe the patient for the following:
● Treatment efficacy
● Treatment tolerability
Adverse events such as allergic or sensitivity reaction to the drug are not usually life-threatening and most can be effectively managed. However, adverse events may be the first signs of potential overdose, which is particularly serious and may lead to death without proper intervention.
Morphine overdose is characterized by respiratory depression or arrest with or without central nervous system depression. Symptoms of central nervous system depression include:
● Dizziness
● Sedation
● Euphoria
● Anxiety
Pupil dilation and/or seizures may also occur during morphine overdose

Patient evaluation
Patient evaluation is the second stage of an intrathecal drug delivery screening test. Patient evaluation usually involves both the patient’s self-evaluation and the clinician’s assessment of the patient’s pain relief. Patient evaluation takes place simultaneously with the screening test when the bolus injection protocol is used. However, although patient evaluation with the continuous-infusion protocol often takes place simultaneously with the screening test, it can also occur later during a patients normal everyday activities. In this case, patients are encouraged to keep a detailed journal of their pain during the time that they are away from the physician. This journal helps to provide an accurate patient evaluation and assists in programming the implanted pump. As determining a patient’s pain relief can be highly subjective, the physician will determine whether the patient has a clinically significant response which is generally considered to be a 50% or greater reduction in pain.
Possible evaluation strategies include:
● Comparing pain scale information before and after the screening test
● A verbal assessment of a patient’s perception of effectiveness
● Looking for signs of increased physical activity
● Reviewing the patients pain journal (if a continuous infusion protocol was used)
Some physicians work with physical therapists during the screening test to evaluate functional improvement in the patients indicative of a clinically significant reduction in pain. In general, if a patient reports at least a 50% reduction in pain with tolerable side effects, it is considered a positive response and the patient
and the physician may decide to proceed with the implantation of a intrathecal drug delivery system. If the screening test was not successful a complete system should not be implanted.

Complete system implant
Complete system implant is undertaken after a positive screening test. Generally, the physician will check for infection in the patient’s body 1–2 days before implant. The implant procedure may be delayed if infection is found. The intrathecal drug delivery system is implanted using a sterile surgical procedure performed under local, regional or general anesthesia. The implantation procedure typically lasts between 1 and 2 hours. The pump is generally implanted subcutaneously in the right or left abdomen where there is sufficient skin and subcutaneous tissue to support the implanted system.
The following implantation procedure is for SynchroMed® EL only.

Preparing the patient
The first step in the implantation procedure is to prepare the patient. The details of this are shown in the table below.

Preparing the pump
Preparation of the pump, especially the purge programming and empty/refill procedures should be completed only when intraspinal access has been achieved with the spinal catheter. Stages in pump preparation are shown in the table below.

Table 3: Preparation of the pump
1.	The initial pump status (the reservoir volume etc) should be checked while the pump is still in the sterile package
2.	The pump should be pre-warmed for 15–20 minutes at 35–40⁰C (or 95–105⁰F) by placing the pump in the blanket warming cupboard
3.	The sterile package should be opened and the pump removed. The pump should be placed in a basin of warm water or saline (35–40⁰C) until purge is complete
4.	When purge is complete, the warm pump should be emptied using a 20 ml syringe and a 22-gauge huber-type needle. The pump should be kept in a warm saline bath during this procedure keeping the water temperature around 35–400C
5.	The pump should be filled with the appropriate amount of prescribed drug using the same 22-gauge huber-type needle
6.	If there is no suture loop, the pump should be placed in a mesh pouch where it is now ready for implantation

Implantation of the catheter and pump
The next step in the implantation process is to implant the catheter and the pump. The physician will carry out the complete system implant procedure by:
● Inserting the 15-gauge Tuohy needle into the lumbar region
● Inserting the catheter through the needle and threading the distal tip of the catheter to the desired location.
● Verifying catheter position using fluoroscopy.
● Making a small vertical incision alongside the Tuohy needle to expose the supraspinous ligament or deep fascia.
● Withdrawing the needle and guidewire
● Preparing the pump pocket by making an incision in the lower abdomen, 2.5 cm beneath the skin.
● Making a subcutaneous tunnel between the spinal incision site to the pump pocket with the tunneling tool
● Tunneling the catheter to the pump pocket and connecting it to the pump.
● Trimming and anchoring the catheter securely.
● Placing the pump in the prepared pocket and closing all the incisions.
After the system is implanted, the patient is transported to the recovery room, where the physician will program the pump. Programming allows the physician to enter the exact protocol for drug delivery and helps to prevent accidental overdose. The pump can then be programmed by the physician as needed during follow-up visits.

Postoperative management
Once the pump is implanted, the patient is closely monitored.
Postoperative care involves the following:
● Management of complications
● Continued patient education
● Dosage adjustment

Surgical complications
Patients who have poor nutritional status, are small in build and/or thin, or who have generally poor health are at greater risk for post-surgical infections. Potential surgical complications include:
● Infection
● Spinal headache
● CSF hygroma (an accumulation of cerebrospinal fluid which produces visible swelling)
● CSF leakage around the catheter insertion site
● Bleeding
● Pain and discomfort
● Pump pocket seroma (an accumulation of fluid in the pump pocket and/or seroma spinal site)
The management of these surgical complications is shown in the
table below.

Table 4: Management of post-surgical complications
Post-surgical issues/problems	Patient management
Wound care	● Patients should change the sterile dressings on the incision site as instructed by their physician ● Patients should comply with hospital policies and procedures regarding would care and infection control
Infections	● Patients should be aware of signs of infection e.g., redness, pain and swelling ● Infections should be treated aggressively with systemic antibiotics ● Infections usually disappear with treatment and rarely necessitate removal of the system ● The pump should be removed promptly if meningeal infection is present or if the reservoir becomes contaminated
CSF leakage	● Patients should be vigilant for CSF leakage at the incision site along the catheter and in the pocket site ● Surgical resuturing or revision may be necessary
Spinal headaches	● Spinal headaches may be caused by CSF leakage around the catheter, or loss of CSF during the implantation procedure ● Oral analgesics can help to reduce pain ● Having the patient lie flat for 1 to 2 days following implantation can greatly reduce the risk of headache
Spinal hygromas (an accumulation of cerebropsinal fluid which produces visible swelling)	● These are typically found under the skin in the lumbar region of the back and result from leakage after intraspinal catheter implantation ● They are typically small and self-limiting and disappear on their own without treatment ● An abdominal binder with pressure dressing at the spinal site may help ● Hygromas may be aspirated, though the risk of infection should first be evaluated
Bleeding	● For patients at high risk of postsurgical bleeding, standard medical practice for postoperative management of patients on anticoagulant therapy should be followed ● Epidural hematomas (swelling from blood accumulation caused by blood vessel breaks) are rare but could produce severe complications ● Patients should be vigilant for signs of epidural hematomas such as severe back pain, sudden onset of leg weakness and spasms, loss of reflexes in distal extremities and loss of bladder/bowel control ● Immediate treatment will be required
Incision pain and discomfort	● Pain and discomfort around the incision site and catheter are common following surgery ● The duration and intensity of pain varies by individual ● Some patients may require ice at tunneling sites ● Mild analgesics e.g. acetaminophen and codeine can be effective
Seromas (an accumulation of fluid in the pump pocket and/or seroma spinal site)	● Seromas may be evident by the first postoperative day ● Signs and symptoms include swelling over the pump site and a feeling of tightness over the pump site ● Pocket seromas often resolve without treatment but may persist for days or even weeks ● If persistent they can be aspirated, though the risk of infection must first be evaluated

System complications
Complications with the infusion system rarely occur but may include:
● Catheter kink
● Catheter obstruction
● Catheter dislodgement, disconnection or breaks
● Programming errors
● Pump failure
System complications may present as drug overdose, loss of drug effect or withdrawal symptoms.

Other complications
In rare instances, the development of an inflammatory mass at the top of the implanted catheter may occur that can result in progressive clinical signs that bear monitoring. These signs include a progressive change in the character, quality or intensity of pain, an increase in the level and degree of pain despite dose escalation and sensory changes e.g., numbness, tingling, burning and hyperesthesia. Presentations that require immediate diagnosis include bowel and/or bladder dysfunction, myelopathy, gait disturbances or difficulty walking and paralysis. If the presence of an inflammatory mass is suspected, evaluation should include a review of the patient history and neurological evaluation, radiological diagnostic procedures e.g. MRI and an appropriate clinical consultation.

Adverse drug events
Patients are monitored until the physician is confident that the patient’s response to the drug is acceptable. Patients need to be aware of the potential averse effects of morphine so that they can immediately communicate any problems to their physician. The most common adverse effects reported with intrathecal morphine include:
● Pruritis (itching)
● Urinary retention
● Constipation
● Headache
● Peripheral edema (excessive fluid retention)

Less frequent, but more serious adverse effects include:
● Respiratory depression
● Myoclonus

Continued patient education
Patients implanted with an intrathecal drug delivery system must maintain a long-term active involvement in their therapy and adhere to lifestyle limitations and precautions. Patients should be instructed to:
● Return for refills at the prescribed time.
● Consult their physician if they notice any unusual symptoms or adverse events
● Notify other healthcare providers of the implanted pump and the medication it contains
● Consult their physician before scheduling any additional therapies or diagnostic tests (e.g., MRI, other drugs)

Patients must also:
● Avoid physical activities that may damage the implant site or system
● Avoid extreme changes of altitude or pressure, which may alter pump flow rates
● Consult with a physician before enjoying saunas or steam baths
● Inform their physician about travel plans to avoid pump emergency refilling and maintenance

Dosage adjustment
The patient’s initial drug dose is determined by monitoring his or her response to the screening trial. However, during the postoperative period, dosage adjustments may be necessary to achieve effective pain management and minimize adverse effects. The upper daily dosage limit for each patient is assessed on an individual basis. Drug dosage is typically changed no more than once per 24 hours.