Trialing

SECTION 1

There are four main types of trialing methods for intrathecal drug delivery (IDD) systems: single-shot intrathecal bolus injection, multiple intrathecal bolus injections, continuous intrathecal infusion, and continuous epidural infusion. All methods demonstrate similar efficacy, and no one method has been proven to be superior for predicting long-term outcomes of IDD⁵⁹. The choice of trialing method is influenced by factors such as the patient’s clinical status, diagnosis, the type of medication used, and the capabilities of the facility and physician preferences¹¹. Currently, major insurance carriers in the USA (Medicare, UnitedHealthcare, and Anthem) and some European countries require a catheter trial for pump implant approval.

Single-Shot Bolus Method

The single-shot bolus method is relatively quick and has a theoretical reduced risk of infection. It can be conducted in an office or outpatient setting. However, this method may have an increased risk of side effects (e.g., nausea, vomiting, diaphoresis, urinary hesitancy), and repeated injections may be necessary to assess the appropriate dose, which can prolong the trial duration.

Continuous Infusion Trialing

Continuous infusion trialing allows for medication titration to achieve efficacy, while providing direct observation of side effects over hours to days. This method is typically conducted in an inpatient setting and may pose a higher risk of infection, but could reduce side effect risks and allow for trialing with multiple medications. It is particularly useful for patients on anticoagulants or with cancer.

Staged Trial

A staged trial involves placing a potentially permanent intrathecal catheter, attaching it to a tunneled extension, and using an external pump for trialing. If the trial is successful, the external extension can be removed, and the intrathecal catheter can be connected to an internal pump. This method is advantageous for patients who have a limited window for trialing and implant (e.g., cancer patients or those on anticoagulants).

Trialing Location and Site-of-Service Issues

Trials can be performed in the office, outpatient ambulatory surgery center (ASC), or hospital settings. Single-shot bolus injections can be safely conducted in outpatient settings, but catheter trials are typically conducted in an inpatient setting¹¹. Medications such as intrathecal fentanyl, ziconotide, bupivacaine, and baclofen may be considered for outpatient trials, if patient risk factors and adequate monitoring are managed appropriately. Inpatient settings are recommended for patients with significant comorbidities or difficulty accessing the intrathecal space¹¹.

Consensus Point 7: When performing an IDD trial, physicians should consider the medication(s) used and patient factors in deciding the setting: inpatient vs outpatient. For catheter trials, an inpatient setting is recommended. USPSTF grade B; level of certainty moderate; evidence level IB.

TRIAL STRATEGIES BASED ON MEDICATION CHOICE

Hydrophilic Medications

Hydrophilic opioids like morphine, hydromorphone, and baclofen diffuse farther in the cerebrospinal fluid (CSF) and have lower systemic uptake compared to lipophilic agents^64,65,66. Therefore, hydrophilic opioids are well-suited for single-shot bolus injections during trialing.

Lipophilic Medications

Lipophilic agents such as fentanyl and bupivacaine do not distribute widely in the CSF and are rapidly taken up systemically^67,68,69. Hence, intrathecal trials with these agents are best accomplished through continuous infusion with the catheter tip placed near the innervation segment of the pain target^70,71.

Consensus Point 8: Physicians should consider pharmacokinetic parameters affecting drug distribution in IDD, especially lipid solubility and systemic effects of drugs cleared from the intrathecal space, particularly for those which are highly lipophilic. USPSTF grade A; level of certainty moderate; evidence level IC.

Ziconotide

Ziconotide is a large hydrophilic peptide that must be administered intrathecally due to its restricted dural distribution¹¹. Continuous infusion trials with ziconotide carry high infection risks if maintained with percutaneous catheters for more than two weeks⁷⁴. Therefore, single-shot boluses may be preferred⁷⁵ and the PRIZM registry study suggests that ziconotide use first-in-pump may result in better analgesia, versus use as an add-on or rescue agent⁷⁹.

Consensus Point 9: Intrathecal trialing of ziconotide may be best performed using injections of small boluses as opposed to continuous infusion. USPSTF grade B; level of certainty moderate; evidence level IB.