The Effect of Measured Radiotherapy Dose on Intrathecal Drug Delivery System Function

ObjectivesRadiation therapy (RT) and intrathecal drug delivery systems (IDDS) are often used concurrently to optimize pain management in patients with cancer. Concern remains among clinicians regarding the potential for IDDS malfunction in the setting of RT. Here we assessed the frequency of IDDS malfunction in a large cohort of patients treated with RT.Materials and MethodsCancer patients with IDDS and subsequent RT at our institution from 2011 to 2019 were eligible for this study. Patients were excluded in the rare event that their IDDS was managed by an outside clinic and follow-up documentation was unavailable. Eighty-eight patients aged 22–88 years old (43% female, 57% male) representing 106 separate courses of RT were retrospectively identified. Patients received varying levels of radiation for treatment of cancer and cumulative dose to the IDDS was calculated. IDDS interrogation was subsequently performed by a pain specialist. Malfunction was recorded as deviation from the expected drug volume and/or device errors reported upon interrogation as defined by the manufacturer.ResultsTotal measured RT dose to the IDDS ranged from 0 to 18.0 Gy (median = 0.2 Gy) with median dose of 0.04 Gy/fraction (range, 0–3.2 Gy/fraction). Ten pumps received a total dose >2 Gy and three received ≥5 Gy. Eighty-two percentage of patients had follow-up with a pain specialist for IDDS interrogation and all patients underwent follow-up with a healthcare provider following RT. There were zero incidences of IDDS malfunction related to RT. No patient had clinical evidence of radiation related pump malfunction at subsequent encounters.ConclusionsWe found no evidence that RT in patients with IDDS led to device failure or dysfunction. While radiation oncologists and pain specialists should coordinate patient care, it does not appear that RT dose impacts the function of the IDDS to warrant significant clinical concern.     

Association Between Oral Pain Medications and Intrathecal Opioid Dose Escalation: A Retrospective Analysis

ObjectivesPatients treated with intrathecal therapy frequently require opioid dose increases to maintain analgesia. The kinetics of intrathecal opioid dose escalation are poorly understood. We hypothesized that antidepressant use, antiepileptic use, and lower baseline oral opioid intake prior to intrathecal pump implantation will be protective against intrathecal opioid dose escalation.Materials and MethodsTargeted drug delivery medication doses were collected from patients who had an intrathecal pump implanted between 2007 and 2016. From a sample size of 136 patients, the association between antidepressant, antiepileptic, and oral opioid use with intrathecal dose escalation was assessed using statistical models.ResultsIndividuals using an antiepileptic had an estimated ratio of means (97.5% CI) of opioid consumption of 0.91 (97.5% CI: [0.48, 1.73], p = 0.74) at six months, 0.83 ([0.43, 1.58], p = 0.51) at 12 months, and 0.77 ([0.40, 1.45], p = 0.36) at 24 months. Patients prescribed antidepressants had an estimated ratio of means (97.5% CI) of 1.43 ([0.77, 2.65], p = 0.19) at six months, 1.41 ([0.76, 2.63], p = 0.22) at 12 months, and 1.33 ([0.70, 2.51], p = 0.31) at 24 months. In our secondary analysis of pre-implant oral opioid use, patients treated with high oral opioid doses had a similar pattern of intrathecal dose escalation when compared to patients using low doses of oral opioids.ConclusionsUse of antiepileptics, antidepressants, or low oral opioid doses was not associated with attenuation of intrathecal dose escalation. Intrathecal opioid dose escalation was observed to occur similarly, regardless of baseline oral analgesics concomitantly employed.     

The Application of Failure Modes and Effects Analysis Methodology to Intrathecal Drug Delivery for Pain Management

ObjectiveThis study aimed to utilize failure modes and effects analysis (FMEA) to transform clinical insights into a risk mitigation plan for intrathecal (IT) drug delivery in pain management.MethodsThe FMEA methodology, which has been used for quality improvement, was adapted to assess risks (i.e., failure modes) associated with IT therapy. Ten experienced pain physicians scored 37 failure modes in the following categories: patient selection for therapy initiation (efficacy and safety concerns), patient safety during IT therapy, and product selection for IT therapy. Participants assigned severity, probability, and detection scores for each failure mode, from which a risk priority number (RPN) was calculated. Failure modes with the highest RPNs (i.e., most problematic) were discussed, and strategies were proposed to mitigate risks.ResultsStrategic discussions focused on 17 failure modes with the most severe outcomes, the highest probabilities of occurrence, and the most challenging detection. The topic of the highest-ranked failure mode (RPN = 144) was manufactured monotherapy versus compounded combination products. Addressing failure modes associated with appropriate patient and product selection was predicted to be clinically important for the success of IT therapy.ConclusionsThe methodology of FMEA offers a systematic approach to prioritizing risks in a complex environment such as IT therapy. Unmet needs and information gaps are highlighted through the process. Risk mitigation and strategic planning to prevent and manage critical failure modes can contribute to therapeutic success.     

Perceived Success and Failure of Intrathecal Infusion Pump Implantation in Chronic Pain Patients

Objectives. Over the past few years, there has been an increased reliance on the intrathecal delivery of drugs for patients suffering from intractable pain. We sought to demonstrate the effectiveness of the intrathecal pain pump by examining self‐reported pre‐ and postimplantation pain levels. Methods. Eighty‐four patients who had elected to implant a Medtronic SynchroMed 1 or 2 system in order to control their pain were asked to complete a survey. The survey consisted of pain ratings before implantation, pain ratings postimplantation, medications used before and after implantation, and patient satisfaction with the procedure. Results. Perceived success rate for implantation is 68%, when measured by the ability to reduce reliance on oral medication. When measured by willingness to undergo the procedure again, the success rate is 86%. Conclusions. Overall, the implantation of an intrathecal pain pump is an effective way for most people to manage their intractable pain and reduce reliance on oral medications.     

Severe Hypertension Following Accidental Clonidine Overdose During the Refilling of an Implanted Intrathecal Drug Delivery System

Background: Complications associated with intrathecal pumps may be linked to the surgical procedure, the implanted device, or the medication itself. Case Reports: Three patients treated chronically with intrathecal clonidine presented with clonidine overdose due to inadvertent extravasation during the refilling procedure. All patients experienced loss of consciousness and severe systemic hypertension that required aggressive parenteral treatment. Discussion: Clonidine is an alpha‐2 agonist with a nearly 100% bioavailability after oral or rectal administration. With high plasma concentration secondary to massive systemic overdose, the specificity for the alpha‐2 receptor is lost and an alpha‐1 agonist activity predominates and causes marked hypertension. Management of clonidine overdose consists of supportive therapy guided by signs and symptoms. Conclusion: Inadvertent injection into the subcutaneous pocket rather than the reservoir is rare but very dangerous as the drug cannot be retrieved and massive doses are involved. Signs and symptoms of systemic overdose with drugs commonly used in implanted drugs delivery system should be well known to ensure early diagnosis and treatment.     

Pump Battery Assessment: Cold,Old, or Dead!

Intraspinal drug delivery systems are becoming increasingly utilized for the management of patients with pain or spasticity. Numerous potential complications associated with the use of this technology have previously been described in the literature. We have had experience with a new complication of the internal alarm being triggered by the instillation of cold solution into the pump resevoir. This new finding could have implications for patients with respect to unnecessary reevaluations of the pump, or possible premature scheduling of pump replacement surgery.     

Managing a National Intrathecal Pump Service During the COVID-19 Pandemic

ObjectiveThe healthcare and social disruption caused by the COVID-19 pandemic could pose significant risk to patients with intrathecal pump (ITP) who may miss refill or replacement appointments. In some cases, this could be life-threatening. We designed and piloted a novel refill protocol to assess its efficacy and safety.Materials and MethodsScreening of our ITP database for patients most at risk of harm was conducted. These patients were risk-assessed for COVID-19 infection and were enrolled in a protocol to optimize the safety and efficiency of their pump replacement or refill.ResultsOf note, 31 of 51 database patients were deemed to be high risk of ITP failure during the pandemic. Thirty patients were successfully refilled with only one patient refusing to leave their house for refill. There were no significant adverse outcomes.ConclusionOur protocol offers a safe and efficient pathway for ITP management during a pandemic.     

Continuous Intrathecal Infusion of a Solution Containing Two Drugs: Calculation Methods

The calculation of the parameters of the pump is complicated for a mixture of two drugs in continuous intrathecal therapy with implantable and programmable pumps. It is important to determine the best proportion of drug solutions to obtain the desired clinical results and also to adapt their proportion to obtain the maximal volume of solution so that the time between two fillings is maximized. This paper proposes mathematical formulas that make easier and faster the calculation of the flow of the pump, the volume of each drug solution to be added to the pump, the concentration of each drug in the mixture, and the duration of the infusion. These values are determined from the desired quantity of each drug to be infused in 24 h, the concentration of each drug solution, and the volume of the reservoir. The calculated values cannot be directly applied because the syringes used to measure the volume of each drug solution have limited accuracy. It is necessary to round the volume of each drug solution and to hold their sum equal to the total volume of the reservoir. All the parameters are then recalculated, and the physician has to choose between several combinations of volumes.     

Acute Exacerbation of Hereditary Coproporphyria Mimics Early Surgical Infection Following Intrathecal Pump Implantation for Chronic Abdominal Pain: A Case Report

Objective: Pain physicians should also be aware of rare complications that can occur after intrathecal pump (ITP) placement. One such rare complication includes an acute exacerbation of hereditary coproporphyria (HCP). Methods: We present a case report that illustrates how an acute exacerbation of HCP can mimic an early surgical post‐procedure infection after ITP implantation. Results: The patient's rapid onset of symptoms two hours after the procedure keyed into HCP as the underlying cause, as acute wound infections rarely occur in the several hours following surgery. After symptomatic treatment of her HCP acute exacerbation, the patient clinically improved without the development of further symptoms or adverse sequelae. She reported considerable pain relief with the implanted drug delivery system. Conclusion: In a setting with multiple confounders, a methodical history and physical examination, close monitoring, and a comprehensive understanding of potential complications can prevent unnecessary ITP extraction and streamline the delivery of appropriate care.     

Intrathecal Morphine Therapy‐Related Granulomas: Faster to Grow than Thought

Complications of intrathecal drug delivery are relatively rare. Of these, infections, cutaneous erosion, and granulomas account for the most common complications. The latter is often noticed when the patient shows signs of sedation and/or reduced pain relief. Granulomas have always been considered to develop over a long period of time, usually calculated in months. Here, we present a case where a catheter‐tip granuloma formed within 5 weeks of intrathecal morphine. The patient was carrying an intrathecal pump for 3 months when it was diagnosed. Probable causes of the formation are discussed.     

Distal Baclofen Pump Catheter Migration Associated with Far‐Lateral Paraspinal Surgical Placement

Objectives. The increased rigidity and spasms implicit to patients being treated with baclofen provide a potential source of drug delivery system–related complications. Placement of the intrathecal catheter from the far‐lateral paraspinal approach has been advocated to avoid catheter fracture as previously reported with a midline approach. A thin fascial layer and increased muscle bulk laterally could increase motion of catheters placed in this position. The authors report on a series of patients found to have spinal catheter migration out from the thecal sac following a far‐lateral paraspinal surgical approach. Materials and Methods. The medical records of six consecutive patients who required revision of an intrathecal baclofen infusion system secondary to spinal catheter migration were included in this retrospective review. Each patient failed to respond to oral antispasmodic therapy and showed a positive response to a trial of intrathecal baclofen before initial pump implantation. Clinical notes and operative reports were reviewed. Results. All patients had a baclofen pump inserted with the intrathecal catheter placed through the far‐lateral portion of the paraspinal musculature entering above the lumbar vertebral pedicle. In all cases, the spinal catheter migrated and was found coiled outside of the thecal sac. In two patients, this occurred on two separate occasions. Mean time to catheter revision following implantation was 7 ± 2 months. Conclusions. Spinal catheter migration from the subarachnoid space can occur with intrathecal baclofen infusion systems. Alternative methods for spinal catheter placement warrant further study.     

The Infection Risk of Intrathecal Drug Infusion Pumps after Multiple Refill Procedures

The objective of this study was to evaluate the long‐term infection risk from refilling intrathecal drug delivery devices. We studied 25 patients (14 females and 11 males) with intrathecal infusion pumps placed for spasticity (23 patients) and chronic pain (two patients). In this study group there were 890 refill procedures (mean 35.6 ± 20.5; range 8–72 times) performed on an outpatient basis by four different physicians. All refill procedures were performed in a sterile and standardized fashion as suggested by the manufacturer, using manufacturer's approved kits for the refills. During the study period, five patients had recurrent infection of the urinary tract and three patients had recurrent infections of the respiratory tract. At the last pump refill of each patient, residual drug, extracted from the pump reservoir, was sent to a laboratory for aerobic and anaerobic cultures. All cultures, in all pumps, were negative for aerobic and anaerobic bacteria. We conclude that periodic refills of intrathecal implanted pumps do not seem to be a risk factor for infection if standard sterile refill procedures are performed. In this study, it was clear that comorbid infections from other parts of the body do not present as a risk for device contamination.     

Programmable Pump for the Administration of Morphine in the Cisterna Magna. A New Approach

The implantation of a drug (opioid) infusion system catheter at the level of the cisterna magna, connected to an implanted programmable pump (Synchromed pump, 8611‐H, Medtronic, Minneapolis, MN) is the procedure we use most commonly for the treatment of craniofacial and upper cervical pain. Our implantation technique, which we consider simple and easy to perform, is discussed in this article. Our results have been extremely encouraging, without untoward effects occurring. Adverse effects are prevented by the close proximity of the catheter tip to the pain receptors.